esophagus Flashcards
1
Q
dysphagia becomes more common with aging and
affects up to
A
15% of persons age 65 or older
2
Q
inability to propel
a food bolus successfully from the hypopharyngeal area through
the upper esophageal sphincter (UES) into the esophageal body is
called
A
oropharyngeal or transfer dysphagia.
Dysphagia
that occurs immediately or within one second of swallowing suggests
an oropharyngeal abnormality
3
Q
Swallowing associated
with a gurgling noise may be described by patients with
A
Zenker diverticulum
4
Q
Most patients with esophageal dysphagia localize their symptoms
to the
A
lower sternum or, at times, the epigastric region. A smaller
number of patients describe a sensation in the suprasternal notch
or higher even though the bolus stops in the lower esophagus
5
Q
Esophageal dysphagia can frequently be relieved by various
maneuvers like
A
repeated swallowing, raising the arms over the
head, throwing the shoulders back, and using the Valsalva maneuver.
6
Q
Causes of Oropharyngeal Dysphagia
A
NEUROMUSCULAR* Amyotrophic lateral sclerosis (ALS, Lou Gehrig disease) CNS tumors (benign or malignant) Idiopathic UES dysfunction Manometric dysfunction of the UES or pharynx† Multiple sclerosis Muscular dystrophy Myasthenia gravis Parkinson disease Polymyositis or dermatomyositis Postpolio syndrome Stroke Thyroid dysfunction
STRUCTURAL Carcinoma Infections of pharynx or neck Osteophytes and other spinal disorders Prior surgery or radiation therapy Proximal esophageal web Thyromegaly Zenker diverticulum
7
Q
Common Causes of Esophageal Dysphagia
A
NEUROMUSCULAR (MOTILITY) DISORDERS Primary Achalasia Distal esophageal spasm Hypercontractile (jackhammer) esophagus Hypertensive LES Nutcracker (high-pressure) esophagus Other peristaltic abnormalities* Secondary Chagas disease Reflux-related dysmotility Scleroderma and other rheumatologic disorders
STRUCTURAL (MECHANICAL) DISORDERS Intrinsic Carcinoma and benign tumors Diverticula Eosinophilic esophagitis Esophageal rings and webs (other than Schatzki ring) Foreign body Lower esophageal (Schatzki) ring Medication-induced stricture Peptic stricture Extrinsic Mediastinal mass Spinal osteophytes Vascular compression
8
Q
Patients who report dysphagia with solids and liquids are more
likely to have an esophageal motility disorder than mechanical
obstruction.
A
Achalasia is the prototypical esophageal motility
disorder;
9
Q
Episodic and nonprogressive dysphagia without weight loss
is characteristic of an
A
esophageal web or a distal esophageal
(Schatzki) ring
10
Q
True dysphagia may be seen in patients with pill, caustic,
or viral esophagitis, but the predominant complaint of patients
with these acute esophageal injuries is usually
A
odynophagia
11
Q
Causes of Odynophagia
A
CAUSTIC INGESTION Acid Alkali PILL-INDUCED INJURY Alendronate and other bisphosphonates Aspirin and other NSAIDs Emepronium bromide Iron preparations Potassium chloride (especially slow-release form) Quinidine Tetracycline and its derivatives Zidovudine INFECTIOUS ESOPHAGITIS Viral CMV EBV HIV HSV Bacterial Mycobacteria (tuberculosis or Mycobacterium avium complex) Fungal Candida albicans Histoplasmosis Protozoan Cryptosporidiosis Pneumocystis jiroveci SEVERE REFLUX ESOPHAGITIS ESOPHAGEAL CARCINOMA
12
Q
is a feeling of a lump or tightness in the throat,
unrelated to swallowing
A
Globus sensation
Globus
sensation is present between meals and swallowing of solids or
large liquid boluses may give temporary relief. Frequent dry
swallowing and emotional stress may worsen this symptom.
Globus
sensation should not be diagnosed in the presence of dysphagia
or odynophagia.
13
Q
The symptom of hiccups (hiccoughs, singultus) is caused by a
combination of
A
diaphragmatic contraction and glottic closure.
Most
cases of hiccups are idiopathic, but the symptom has been associated
with many conditions (trauma, masses, infections, uremia)
that affect the central nervous system, thorax, or abdomen.
chlorpromazine, nifedipine, haloperidol, phenytoin, metoclopramide,
baclofen, and gabapentin
14
Q
Esophageal chest pain is usually described as a
A
squeezing or
burning substernal sensation that radiates to the back, neck, jaw,
or arms.
15
Q
day trial
of an oral PPI taken twice daily has been shown to be sensitive
and specific for the diagnosis of esophageal chest pain when compared
with ambulatory intraesophageal pH testing
A
A 10- to 14-
If a patient fails this trial, the next practical approach may
be a trial of agents such as imipramine or trazodone that raise the
pain threshold
16
Q
Extraesophageal Manifestations of GERD
A
Asthma Chronic cough Excess mucus or phlegm Globus sensation Hoarseness Laryngitis Pulmonary fibrosis Sore throat
17
Q
Dyspepsia is derived from the Greek words “δυς-” (dys-) and
“πέψη” (pepse) and literally means
A
“difficult digestion.” In current
medical terminology, dyspepsia refers to a heterogeneous group of
symptoms in the upper abdomen.
18
Q
Only 4 symptoms
are now considered to be specifically of gastroduodenal origin
A
(postprandial fullness,
early satiation, and epigastric pain or epigastric burning)
19
Q
refers to dyspeptic symptoms in persons in whom diagnostic
investigations have not yet been performed and in whom a specific
diagnosis that explains the dyspeptic symptoms has not been
determined.
A
uninvestigated dyspepsia
20
Q
The risk of esophageal cancer is increased in
A
men,
smokers, persons with high alcohol consumption, and those with
long-standing heartburn
21
Q
Diagnostic criteria* for
functional dyspepsia†
A
1. One or more of the following: Bothersome postprandial fullness Bothersome early satiation Bothersome epigastric pain Bothersome epigastric burning AND 2. No evidence of structural disease (including at EGD) that is likely to explain the symptoms
Criteria fulfilled for the previous 3 months with symptom onset at least 6 months prior to diagnosis
22
Q
Diagnostic criteria* for
postprandial distress
syndrome (PDS)
A
Must include one or both of the following at least 3 days a week:
1. Bothersome postprandial fullness (i.e., severe enough to impact usual activities)
2. Bothersome early satiation (i.e., severe enough to prevent finishing a regular-sized meal)
3. No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations
(including at EGD)
Supportive Criteria
1. Postprandial epigastric pain or burning, epigastric bloating, excessive belching, and nausea can also be present
2. Vomiting warrants consideration of another disorder
3. Heartburn is not a symptom of dyspepsia but often may coexist with PDS
4. Symptoms that are relieved by evacuation of feces or gas should generally not be considered part of the
dyspepsia symptom complex
5. Other individual digestive symptoms or groups of symptoms (e.g., from GERD or IBS) may coexist with PDS
23
Q
Diagnostic criteria* for epigastric pain syndrome (EPS)
A
Must include one or both of the following symptoms at least 1 day a week:
1. Bothersome epigastric pain (i.e., severe enough to impact on usual activities)
2. Bothersome epigastric burning (i.e., severe enough to impact usual activities)
No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations
(including at EGD).
Supportive Criteria
1. Pain may be induced by ingestion of a meal, relieved by ingestion of a meal, or may occur while fasting
2. Postprandial epigastric bloating, belching, and nausea can also be present
3. Persistent vomiting likely suggests another disorder
4. Heartburn is not a symptom of dyspepsia but may often coexist with EPS
5. The pain does not fulfill criteria for biliary pain
6. Symptoms that are relieved by evacuation of feces or gas generally should not be considered part of the
dyspepsia symptom complex
7. Other digestive symptoms (such as GERD and IBS) may coexist with EPS
24
Q
, defined as abnormally enhanced perception
of visceral stimuli, is considered one of the major pathophysiologic
mechanisms in functional GI disorders
A
Visceral hypersensitivity
25
In a
population with a high prevalence (>20%) of Hp infection, the
test-and-treat approach remains attractive because patients with
PUD will be cured.
The tests of choice are the urea breath test
| or the fecal antigen test.
26
constructed as an 18- to 26-cm long hollow
muscular tube with an inner “skin-like” lining of stratified squamous
epithelium
The esophagus
27
Between swallows the esophagus is
collapsed, but the lumen distends up to 2 cm anteroposteriorly and
3 cm laterally to accommodate a swallowed bolus. Structurally, the
esophageal wall is composed of
4 layers: innermost mucosa, submucosa,
muscularis propria, and outermost adventitia; unlike the
remainder of the GI tract, the esophagus has no serosa
28
The muscularis propria is responsible for carrying out the organ’s
motor function.
The upper 5% to 33% is composed exclusively of
| skeletal muscle, and the distal 50% is composed of smooth muscle.
29
Proximally, the esophagus
begins where the inferior pharyngeal constrictor merges with
the cricopharyngeus, an area of skeletal muscle known functionally
as the
upper esophageal sphincter (UES)
The UES
is contracted at rest and, hence, creates a high-pressure zone that
prevents inspired air from entering the esophagus. Below the UES,
the esophageal wall is composed of inner circular and outer longitudinal
layers of muscle
30
The esophageal body
| lies within the posterior mediastinum behind the
trachea and left mainstem bronchus and swings leftward to pass behind the heart
and in front of the aorta.1
31
At the T10 vertebral level the esophageal
body leaves the thorax through a hiatus located within the right
crus of the diaphragm (see Fig. 43.1).
Within the diaphragmatic
hiatus the esophageal body ends in a 2- to 4-cm length of asymmetrically
thickened circular smooth muscle known as the lower
esophageal sphincter (LES
32
The venous
drainage of the upper esophagus is through the superior vena
cava,
the midesophagus through the azygos veins, and the distal esophagus through the portal vein by means of the left and short gastric veins.
The submucosal venous anastomotic network of the
distal esophagus is important because it is where esophageal varices emerge in patients with portal hypertension
33
The lymphatic system of the esophagus is also segmental; the
| upper esophagus drains to the deep cervical nodes,
the midesophagus
to the mediastinal nodes, and the distal esophagus to the celiac
and gastric nodes
34
multilayered epithelium consists of 3 functionally distinct layers: stratum corneum, stratum spinosum, and stratum germinativum
The upper esophagus is supplied by branches of the superior
and inferior thyroid arteries, the midesophagus by branches of
the bronchial and right intercostal arteries and descending aorta,
and the distal esophagus by branches of the left gastric, left inferior
phrenic, and splenic arteries
35
In the most common TEF, the trachea communicates with the distal
segment of the atretic esophagus (B).
The next most common type is
the H-type TEF, in which the trachea communicates with an otherwise
normal esophagus
Esophageal atresia occurs as an isolated anomaly in only 7%
of cases; the rest are accompanied by a form of tracheoesophageal
fistula, most often (89%) a distal-type fistula (see Fig. 43.7B) and
rarely (3%) the H-type fistula
36
Dysphagia lusoria is the term given for symptoms arising from
vascular compression of the esophagus by an aberrant right subclavian
artery
```
A, Interface between lumen and mucosa;
B, mucosa;
C, submucosa;
D, muscularis propria;
E, adventitia.) Note that
```
A, C, and E are hyperechoic, and
B and D are hypoechoic.
37
The distal esophagus may contain 2 “rings,” the A and B (Schatzki)
ring, that demarcate anatomically the proximal and distal borders
of the esophageal vestibule.
```
The A (muscular) ring is located at the
proximal border (see Fig. 43.3). It is a broad (4 to 5 mm) symmetrical
band of hypertrophied muscle that constricts the tubular esophageal
lumen at its junction with the vestibule
```
In this location the A
ring, which is covered by squamous epithelium, corresponds to the
upper end of the LES.55 The A ring is rare,
38
Symptomatic A rings can be treated by
passage of
a large-caliber mercury-weighted esophageal dilator, injection of
botulinum toxin, or by peroral endoscopic myotomy
39
The B ring, otherwise known as the mucosal or Schatzki ring,
is very common, and found in 6% to 14% of subjects having a
routine upper GI series
On
barium study it is always found in association with a hiatal hernia
and is recognized as a thin (2-mm) membrane that constricts
the esophageal lumen at the junction of the vestibule and gastric
cardia
40
The Schatzki ring has squamous epithelium
on its upper surface and columnar epithelium on its lower surface
and so demarcates the squamocolumnar junction.
The ring itself
is composed of only mucosa and submucosa; there is no muscularis
propria. Schatzki rings can be congenital or acquired, and a
relationship to GERD is likely
41
Most B rings are asymptomatic, yet when the diameter of the
| esophageal lumen is narrowed to
13 mm or less, rings commonly are
the cause of intermittent dysphagia for solids or unheralded acute
solid-food impactions
42
are developmental anomalies characterized by
1 or more thin horizontal membranes of stratified squamous epithelium
within the upper (cervical) esophagus and midesophagus
Esophageal webs
Unlike rings, these anomalies rarely encircle the lumen but
instead protrude from the anterior wall, extending laterally but
not to the posterior wall
Webs are
fragile membranes and so respond well to esophageal bougienage
with mercury-weighted dilators.
43
refers to the appearance on endoscopy of a small
(0.5 to 2 cm) distinctive, velvety red island of heterotopic gastric
mucosa amid a lighter pink squamous mucosa, generally localized
immediately below the UES
inlet patch
44
In rare instances, an inlet patch is found in association
with an esophageal web or stricture74 or ulcer, the latter
resulting in bleeding or perforation.69
Adenocarcinoma arising
in an inlet patch is a rare complication, although there is a statistically
significant association between inlet patches and proximal
esophageal adenocarcinomas
45
Diverticula are outpouchings from tubular structures. True diverticula
involve all layers of the intestinal wall, whereas
false diverticula
are due to herniation of mucosa and submucosa through
the muscular wall
True diverticula are often assumed to
be congenital lesions, and false diverticula are assumed to be
acquired, but this is not always the case. Some authors reserve the
terms false diverticula or pseudodiverticula for diverticula caused by
an inflammatory process.
46
The prevalence of Zenker diverticula has been estimated to
| be between 0.1% and 0.01%.
Patients generally present in the
seventh or eighth decade of life. Twice as many men as women
develop Zenker diverticula
47
Zenker diverticula are acquired. They develop when abnormally
high pressures occur during swallowing, leading to mucosa
that protrudes through an area of anatomic weakness in the pharynx
known as
Killian triangle (`
48
Killian triangle is
| located posteriorly where the
transverse fibers of the cricopharyngeus
muscle of the upper esophageal sphincter (UES) intersect
with the oblique fibers of the inferior pharyngeal constrictor
muscle.
With a Zenker diverticulum, opening of the UES is impaired,
generating high pressures with swallowing
49
are seen just below the
cricopharyngeus and have a similar presentation to Zenker
diverticula.
Killian-Jamieson diverticula
50
, a palpable nodule or swelling on the left anterior
| neck that may gurgle on palpation, can be found
Boyce sign
51
Zenker diverticulum can be suspected from a careful history.
Barium swallow is the most useful diagnostic study
Barium swallow in the lateral
view using video fluoroscopy is helpful for detecting small
diverticula
52
During endoscopy, Zenker diverticulum should be
| suspected if, on entering the pharynx, the UES cannot be located.
In such cases, the endoscopy should be stopped, and the patient
sent for a barium study.
53
Presenting Symptoms in Patients with a Zenker
| Diverticulum
```
Aspiration
Choking
Dysphagia
Halitosis
Regurgitation
Voice changes
Weight loss
```
54
Squamous cell cancer may develop in Zenker diverticula;
the estimated
| incidence is 0.4% to 1.5%.
55
Zenker diverticula may be treated by open surgical procedures
or by transoral endoscopic techniques using rigid or flexible
endoscopes
Open surgery for Zenker diverticula is typically performed
through the left neck in patients with large (>5 cm) diverticula
that extend into the thorax
56
Large diverticula can be resected, inverted, or suspended (diverticulopexy).
Cricopharyngeal myotomy is performed to treat
the hypertonic cricopharyngeus muscle, and is the key aspect to
treating this disorder; the hypertonic cricopharyngeus muscle
must be divided to relieve distal obstruction.
57
If diverticula are
| resected without myotomy,
there is an increased risk of postoperative
| leaks and an increased frequency of recurrence.
58
Complications
of open surgery include anastomotic leaks, mediastinitis,
esophagocutaneous fistula, and vocal cord paralysis from injury to
the recurrent laryngeal nerve, which runs in the tracheoesophageal
groove.
Endoscopic treatment of Zenker diverticulum can be performed
using a rigid endoscope or flexible endoscope, with
division of the fibrotic septum between the esophagus and the
diverticulum
Endoscopic
techniques are suitable for patients with medium-sized
diverticula (2 to 5 cm).
59
This septum is composed of
the posterior wall of the esophagus and the anterior wall of the
diverticulum and includes the UES.
The muscular layers of this
| septum (and UES) are incised, restorating a single lumen.
60
Traction diverticula are related to an inflammatory,
| fibrotic, or neoplastic process outside of the esophagus.
Traction
diverticula are often related to mediastinal inflammation associated
with tuberculosis or histoplasmosis
61
Pulsion diverticula are typically caused by motility
disorders.
The most common type of pulsion diverticula is an epiphrenic
diverticula, which is located near the diaphragmatic hiatus (
About 80% of epiphrenic diverticula are associated with esophageal motility disorders such as achalasia or distal esophageal
spasm,
62
Epiphrenic
diverticula have been reported as a complication of band-based
obesity surgery,
due to obstruction of the esophagus and upper
| stomach by the band
63
Squamous cell carcinoma has been reported in epiphrenic diverticula.
44,45
As with Zenker diverticula, accumulation of radioactive
iodine tracer in esophageal diverticula has been mistaken for metastatic thyroid cancer
To prevent gastroesophageal
reflux after myotomy, a partial posterior (Toupet) or
anterior (Dor) fundoplication may be performed.
64
EIP most commonly in their sixth or seventh decades. The condition
is slightly more common in men than in women.54
EIP are abnormally dilated ducts of submucosal glands. They
are thought to be acquired and are often associated with conditions
that cause chronic esophageal inflammation.
65
A hernia is a protrusion of an organ or structure into an opening
or pouch. Abdominal wall hernias protrude through the muscular
and fascial walls of the abdomen and have 2 parts:
(1) the orifice or defect in the aponeurotic wall of the abdomen, and (2) the hernia sac, which consists of peritoneum and abdominal, contents.
66
Abdominal wall hernias are external if the sac protrudes
through the abdominal wall or interparietal if the sac is contained
within the abdominal wall.
Internal hernias are contained within
| the abdominal cavity and do not always have a hernia sac
67
Hernias are reducible when the protruding contents can be
returned to the abdomen and irreducible or incarcerated when
they cannot.
A hernia is strangulated when the vascular supply
| of the protruding organ is compromised,
68
where only one side of the bowel (most often the antimesenteric
side) protrudes through the hernia orifice.
Richter hernia,
69
3 main types of diaphragmatic hernias:
hiatal and paraesophageal
hernias (both involve the hiatus), congenital hernias,
and traumatic hernias
most common diaphragmatic hernias are sliding hernias
of the stomach through the esophageal hiatus hiatal and paraesophageal hernias.
70
Sliding hiatal hernias (type I) occur when the gastroesophageal
junction and some portion of the stomach are displaced above the
diaphragm, but the orientation of the stomach axis is unchanged.
The frequency of sliding hiatal hernias increases with age. The
phrenoesophageal membrane anchors the gastroesophageal junction
to the diaphragm
Hiatal hernias
may be caused by age-related deterioration of this membrane,
combined with normal positive intra-abdominal pressure and
traction of the esophagus on the stomach as the esophagus shortens
during swallowing
71
```
Paraesophageal hernias (type II) occur when the stomach protrudes
through the esophageal hiatus alongside the esophagus (Fig.
27.1A).
```
The gastroesophageal junction remains in a normal position
at the level of the diaphragm, because there is preservation
of the posterior phrenoesophageal ligament and normal anchoring
of the gastroesophageal junction, and only the stomach moves
proximally
72
Most paraesophageal hernias contain a sliding hiatal component
in addition to the paraesophageal component and are thus
| mixed diaphragmatic hernias (type III
73
other intra-abdominal structures (e.g.,
| omentum, colon, spleen) may also herniate
(type IV
cross
sectional imaging with CT scan will be the test of choice to document
a type IV defect, as the barium study may not reveal adjacent
colon or pancreas through the hiatus.
74
Does the gastroesophageal junction lie at or
above the hiatus? (2) Does the stomach or any other visceral structure
lie above the gastroesophageal junction?
For example, if the
gastroesophageal junction is above the hiatus and there is stomach
above it, the patient has a type III (mixed) hernia
75
14% to 84% of patients examined, depending on the
| patient population, method of diagnosis, and symptoms present.
In general, hiatal hernias are more frequent in patients
with GERD.
About 90% to 95% of hiatal hernias found by
radiograph are sliding (type I) hernias; the remainder are paraesophageal hernias.
76
With chest radiography, a hiatal
hernia may be noted as a soft tissue density or an air-fluid level in
the retrocardiac area
Hiatal hernias are sometimes diagnosed on
| UGI barium studies.
77
Cameron lesions or linear erosions may develop in patients
| with sliding hiatal hernias, particularly large hernias
These mucosal lesions are usually found on the lesser curve
of the stomach at the level of the diaphragmatic hiatus
This is the location of the rigid anterior margin of the
hiatus formed by the central tendon of the diaphragm
Cameron lesions may cause acute or chronic UGI bleeding with a
poor response to acid suppression therapy.14 Iron deficiency anemia
due to chronic bleeding is seen in 30% to 40% of patients
with paraesophageal hernia
78
Gastric volvulus is a life-threatening complication of paraesophageal
hernia.
Symptoms include acute abdominal pain and
| retching, and it can progress rapidly to a surgical emergency (
79
Simple sliding hiatal hernias do not require treatment, unless
symptomatic from reflux (see Chapter 46). Patients with symptomatic
giant sliding hiatal hernias, paraesophageal, or mixed
hernias should be offered surgery.
When closely questioned, most
| patients with type II, III, or IV hernias will have symptoms
80
motility disorders, the surgeon may elect to perform
| a loose anterior wrap
(Dor fundoplication) or use a gastrostomy
| tube or gastropexy to fix the stomach intra-abdominally
81
The principles of surgery for repair of hiatal or paraesophageal
hernias include 4 main elements:
(1) reduction of the hernia
from the mediastinum or chest, with excision of the hernia
sac; (2) reconstruction of the diaphragmatic hiatus, with simple
posterior closure with or without bolstering with prosthetic
mesh; (3) providing bulk at the hiatus to prevent prolapse into
the chest with a fundoplication, which can lessen postoperative
reflux; and (4) addition of a gastropexy or gastrostomy tube to
provide an additional tacking mechanism for the stomach intraabdominally.
82
Patients with sliding hiatal or paraesophageal hernias may have
shortening of the esophagus. This makes it difficult to restore the
gastroesophageal junction below the diaphragm without tension,
a key factor in decreasing recurrence.
In such cases, an extra length
of neoesophagus can be constructed from the proximal stomach
(Collis-Nissen procedure
83
Recurrence is higher in obese patients and many will favor a
Roux-en-Y gastric bypass (RYGB) procedure in those that have a
BMI greater than 35kg/m2
84
Hernias manifesting in neonates are most often
Bochdalek
The key finding is a posterior
chest mass, as the defect of Bochdalek is posterior
Morgagni hernias are anterior,
85
are ingested materials (food or
| other materials) that accumulate in a normal or abnormal stomach.
Bezoars
86
The most common patient group that unintentionally ingests
| foreign bodies is children, particularly those between
ages 6 months and 3 year
Children account for 80% of true foreign body ingestions
Coins are the most common objects swallowed by children, but
other frequently swallowed objects include marbles, small toys,
crayons, nails, and pins
87
The most common groups that intentionally ingest foreign
| bodies are
psychiatric patients and prisoners,21 in whom ingestion
| is often done for secondary gain
88
The vast majority (75% to 100%) of patients with
| an esophageal food impaction have an underlying predisposing
esophageal pathology,25,26 most often peptic strictures, Schatzki
rings, and increasingly eosinophilic esophagitis (EoE
Food impactions most commonly occur in adults in their
fourth or fifth decade of life but are becoming more prevalent
in young adults because of the rising incidence of eosinophilic
esophagitis
89
```
The majority (≈ 80% to 90%) of GIFBs pass through the GI tract
without any clinical sequelae and cause no harm to the patient.1,35
```
The remaining 10% to 20% of GIFBs will require endoscopic
| intervention, and 1% of GIFBs may require operative therapy.
90
The pharynx is the first area where foreign bodies
| may become entrapped and cause complications.
In the hypopharynx,
short sharp objects like fish bones and toothpicks may
lacerate the mucosa or become lodged
91
Once in the esophagus, there are 4 areas of narrowing where
| food boluses and foreign bodies become lodged:
upper esophageal
sphincter, level of the aortic arch, level of the mainstem
bronchus, and esophagogastric junction
These areas all have
luminal narrowing to 23 mm or less.4
92
Foreign body and food impaction in the esophagus
have the highest incidence of overall adverse events, with the
complication rate directly proportional to how long the object is
lodged in the esophagus.
Esophageal foreign bodies in children
have a significantly lower spontaneous passage rate, as low as 12%
compared with other GIFBs
93
```
Large objects (>2.5 cm [1 inch] in diameter) may not be able
to pass through the pylorus.
```
Long objects (>5 cm [2 inches]) such
as pens, pencils, and eating utensils may not negotiate around the
duodenal sweep or through the pylorus
94
Inserted rectal objects are often tenaciously retained because
of anal sphincter spasm and edema, making spontaneous passage
of the object difficult.
The angulation and valves of Houston may
| also impede passage of objects through the rectum.
95
Diagnostic upper endoscopy for foreign bodies is relatively
contraindicated when there are clinical or radiographic signs
of perforation. Once an ingested foreign object has passed the
ligament of Treitz, endoscopy is generally not indicated, because
these objects will typically pass unimpeded with notable exceptions
(see later).
Similarly, most small (<2.5 cm) blunt objects in
an adult patient’s stomach do not require endoscopic retrieval;
most will pass without complication
96
80% to 90% of GIFBs will spontaneously pass through
| the GI tract without complication
smooth muscle relaxant glucagon is the most widely used and
studied drug for the treatment of esophageal food and foreign
object impactions. Glucagon, given in intravenous doses of 0.5 to
2 mg, can produce relaxation of the lower esophageal sphincter
Nifedipine and nitroglycerin are not recommended because of
hypotension-related side effects and questionable efficacy.
97
Ideally, no object should be left in the esophagus
| longer than
24 hours.
Objects longer than 5 cm and round objects wider
than 2.5 cm also may not be passed and should be removed from
the stomach with an endoscope at presentation or if they have
not progressed in 3 to 5 days.
98
More than 75% of patients with food impactions have associated
esophageal pathology,5,26 and about half of patients with food bolus impactions have abnormal 24-hour esophageal pH
studies and/or esophageal manometry.
If an esophageal stricture
or Schatzki ring is present after the food bolus is cleared, it can
be safely and effectively dilated concurrently if circumstances
allow. More often, mucosal abrasions or erythema from the food
dwelling in the esophagus for an extended period exists, and dilation
is delayed for 2 to 4 weeks, during which patients should
be prescribed proton pump inhibitor therapy
99
Sharp and pointed objects may cause a perforation in up to
15% to 35% of patients and account for one third of all perforations
from GI foreign bodies, with a 2.5-fold greater risk of
complications compared to other GIFB
Sharp and pointed objects retained in the esophagus are considered
a medical emergency and should be removed within 6 to 12 hours.
100
Ingested objects longer than 5 cm (2 inches), especially those
longer than 10 cm (4 inches), have difficulty passing through
the pylorus and duodenal sweep and can get hung up, causing
obstruction or perforation at these locations
Long objects should be grasped at one end
and oriented longitudinally to permit removal. For extraction of
long objects, use of the 60-cm overtube endoscope assembly, as
described earlier, should be considered
101
In adults, the pylorus will allow passage of most blunt
objects up to 25 mm in diameter, which includes all coins except
half-dollars (30 mm) and silver dollars (38 mm
once
in the stomach, a regular diet is appropriate, with radiographic
monitoring every 1 to 2 weeks to confirm progression or elimination.
If after 3 to 4 weeks a blunt object has not passed, endoscopic
removal should be performed.
102
Half of patients with disc batteries in the stomach have
mucosal damage and thus gastric batteries should also be removed
via the endoscope.127 Once in the small intestine, disc batteries
rarely cause clinical problems and can be observed radiographically,
with 85% passing through the GI tract within 72 hours
Body stuffers
are drug users or traffickers who quickly ingest small amounts
of drugs, but in poorly wrapped or contained packages that are
prone to leakage. Body packers are “mules” used by drug smugglers
for drug transport; they ingest large quantities of carefully
prepared packages intended to withstand GI transit
103
Bezoars are collections of indigestible material that accumulate in
the GI tract, most frequently in the stomach.
The 3 most common
types of bezoars encountered are phytobezoars, composed
of vegetable matter; trichobezoars, made up of hair or hair-like
fibers; and medication bezoars (pharmacobezoars)
Phytobezoars are the most common type of bezoar. Offending
fruits and vegetables include celery, pumpkin, prunes, raisins,
leeks, beets, and persimmon
104
is a term
used to describe trichobezoars located primarily in the stomach
that extend past the pylorus and into the duodenum, causing
bowel obstruction or even jaundice or pancreatitis because of
obstruction at the level of the ampulla of Vater.
Rapunzel syndrome
105
Alkaline ingestion causes a liquefactive necrosis that very rapidly
extends through the mucosa, submucosa, muscularis of the
esophagus, and stomach
Vascular thrombosis occurs following
| the necrosis.
106
Acidic agents cause a coagulative necrosis, with thromboses of
mucosal blood vessels and a more limited superficial necrosis.
Acidic agents are more apt to damage the stomach, particularly the antrum, more than the esophagus
With alkali ingestion, the esophagus is most
affected; neutralization by gastric acid limits damage in the stomach.
Acidic agents tend to be ingested in smaller quantities because of their offensive
taste and immediate pain, so they are associated with less overall damage than alkali agents.
107
TABLE 28.1 Endoscopic Grades of Caustic Injury
Grade Endoscopic Findings
Grades
I and IIA burns, which correspond to first- and second-degree burns, will usually heal without sequelae.
I Edema and erythema
IIA Hemorrhage, erosions, blisters, ulcers with exudate
IIB Circumferential ulceration
III Multiple deep ulcers with brown, black, or gray discoloration
IV Perforation
strictures will develop in 70% to 100% of patients with grade IIB injury, which causes circumferential ulceration, and grade III injury with
associated necrosis.
Grade IV injury with perforation carries a
mortality rate of up to 65% and requires urgent surgery
108
Up to one third of caustic ingestion patients will develop esophageal
stricture after initial recovery (see Fig. 28.13)
Stricture formation presents most commonly at 2 months after injury but can occur at any time from 2 weeks to many years after the initial injury.
Perforation
24-72 hours
Endoscopic injection of triamcinolone into the stricture or use of topical mitomycin has been reported to be beneficial in treating caustic strictures
109
Alkaline caustic ingestion, in particular, is associated with an
increased risk for squamous cell cancer of the esophagus.
atients
with a history of lye ingestion have a 1000-fold increased risk
of developing esophageal cancer, with a lag time from injury of
approximately 40 years
110
is the most specific to the eosinophil lineage and is
| responsible for the selective differentiation of eosinophils
IL-5
hypereosinophilic syndrome (HES)121; this syndrome is defined
by sustained, severe peripheral blood eosinophilia (>1500 cells/
mm3) and the presence of end organ involvement in the absence of
known causes for eosinophilia
111
EoE representing the second most common
| cause of chronic esophagitis.
The etiology of EoE is poorly
understood, but food allergy has been implicated as a primary
contributor.
112
The diagnostic criteria for EoE in 2011,83 emphasized
| that EoE requires finding
15 or more eosinophils/HPF
(peak value) in the esophagus. This definition is based on a 2017
consensus recommendation that PPI-responsiveness is not considered
in the diagnosis of EoE, as PPI-REE has phenotypic,
genetic, and molecular features that overlap with PPI-resistant
esophageal eosinophilia.
With few exceptions, 15 eosinophils/
HPF (peak value) is considered a minimum threshold for a diagnosis
of EoE.
113
Solid-food dysphagia
| continues to be the most common presenting symptom.142
Food
impaction necessitating endoscopic bolus removal occurs in 33%
to 54% of adults with EoE
presence of 15 or more eosinophils/HPF,
dilated intercellular spaces and in some cases also elongated
papillae, and inflammation and fibrosis in the lamina propria
114
Endoscopic Eosinophilic Esophagitis Reference Score
EoE
Major Features
Edema
(Also referred to as decreased vascular markings, mucosal pallor)
Grade 0: Absent. Distinct vascularity present
Grade 1: Loss of clarity or absence of vascular markings
Fixed rings
(Also referred to concentric rings, corrugated esophagus, corrugated
rings, ringed esophagus, trachealization)
Grade 0: None
Grade 1: Mild-subtle circumferential ridges
Grade 2: Moderate-distinct rings that do not impair passage of a
standard diagnostic adult endoscope (outer diameter 8-9.5 mm)
Grade 3: Severe-distinct rings that do not permit passage of a
diagnostic endoscope
Exudates
(Also referred to as white spots, plaques)
Grade 0: None
Grade 1: Mild-lesions involving less than 10% of the esophageal surface area
Grade 2: Severe-lesions involving greater than 10% of the esophageal
surface area
Furrows
(Also referred to as vertical lines, longitudinal furrows)
Grade 0: Absent
Grade 1: Vertical lines present
Stricture
Grade 0: Absent
Grade 1: Present (specify estimated luminal diameter)
Minor features
Crepe paper esophagus
(Mucosal fragility or laceration upon passage of diagnostic endoscope
but not after esophageal dilation)
Grade 0: Absent
Grade 1: Present
Narrow-caliber esophagus
(Reduced luminal diameter of the majority of the tubular esophagus)
Grade 0: Absent
Grade 1: Present
115
histologic scoring system
(HSS) for EoE was validated. In addition to identifying 15 or
more eosinophils/HPF, 8 other histologic features were shown
to differentiate treated from untreated patients and that the HSS
outperforms esophageal eosinophil levels for disease diagnosis
and monitoring.
The 8 HSS features include eosinophil density,
basal zone hyperplasia, eosinophil abscesses, eosinophil surface
layering, dilated intercellular spaces, surface epithelial alteration,
dyskeratotic epithelial cells, and lamina propria fibrosis. Severity
and extent are scored using a 4-point scale, with 0 being normal
and 3 denoting maximum change
116
Up to 7 eosinophils/HPF (400×) is most indicative of GERD, 7
to 15 eosinophils/HPF likely represents a combination of GERD
and food allergy,
and at least 15 eosinophils/HPF is characteristic
of EoE.
dietary therapy, topical glucocorticoids, and a PPI
117
The practice
of gradual esophageal dilation with a target goal of 15 to 18 mm
and of limiting the progression of dilation diameter per session to
3 mm or even less if resistance is encountered is reasonable but
has not been specifically addressed in patients with EoE
118
When using
topical glucocorticoids in the form of fluticasone, a metered-dose
inhaler without a spacer has been advocated83;
alternatively, a
slurry of budesonide (in the form used for nebulizers) with sucralose
(Splenda) also has been recommended
119
PPI therapy can establish histologic remission and symptom
The duration of untreated EoE is a good predictor of
stricture risk
amelioration in 50% and 60% of EoE patients, respectively
The 2017 European guidelines use high-dose PPI for 8 weeks as a
first line in the treatment algorithm for EoE.
120
EG can
| be diagnosed when at least 30 eosinophils/HPF is identified in
at least 5 distinct HPFs in the stomach19
The
mucosal form of EGE, the most common variant, is characterized
by vomiting, abdominal pain that can even mimic acute
appendicitis, diarrhea, blood loss in the stools, iron-deficiency
anemia, malabsorption, protein-losing enteropathy, and failure
to thrive.193,208 The muscularis form is characterized by infiltration
of eosinophils predominantly in the muscularis layer, leading
to thickening of the bowel wall, which may result in symptoms
of GI obstruction mimicking pyloric stenosis or other causes of
gastric outlet obstruction. The serosal form occurs in a minority
of patients with EGE, and it is characterized by exudative ascites
with higher peripheral eosinophil counts compared with the
other forms
121
Acute esophageal injury is believed to be primarily
related to radiation damage to the basal epithelial layer, manifested
histologically by vacuolization, resulting in epithelial thinning
followed by denudation
These changes manifest clinically as dysphagia, odynophagia, and substernal discomfort, usually occurring within 2 to 3 weeks following initiation of RT
Abnormal peristalsis has
been reported at 1 to 3 months following treatment completion,
whereas most strictures occur 4 to 8 months following treatment
completion. Late effects are usually not seen until 3 months
following completion of RT
Complete epithelial recovery from radiation effects may take 3 to 24 months
122
It is estimated that approximately half of patients receiving upper
abdominal radiation will experience emesis
within 2 to 3 weeks
| following radiation initiation
123
Late effects of gastric irradiation have been classified into 4
categories:
(1) acute ulceration (occurring shortly after completion
of RT); (2) gastritis with smoothened mucosal folds and
mucosal atrophy on endoscopy, accompanied by radiographic
evidence of antral stenosis (1 to 12 months following irradiation)
(see Chapter 52); (3) dyspepsia, consisting of vague gastric symptoms
without obvious clinical correlate (6 months to 4 years following
irradiation); and (4) late ulceration (averaging 5 months
after irradiation)
124
The nasopharynx extends from the
| base of the skull to the distal edge of the soft palate.
Muscles in
the nasopharynx elevate the soft palate during swallowing, seal
the nasopharynx, and prevent nasopharyngeal regurgitation.
The
oropharynx extends from the soft palate to the base of the tongue.
The inferior margin of the oropharynx is demarcated by the valleculae
anteriorly and the mobile tip of the epiglottis posteriorly
125
The esophagus is a 20- to 22-cm tube composed of skeletal and
smooth muscle.
The proportion of each muscle type is species
dependent, but in humans, the proximal 5% is striated, the middle 35% to 40% is mixed with an increasing proportion of
smooth muscle distally, and the distal 50% to 60% is entirely
smooth muscle
126
The outer longitudinal muscle arises from the
cricoid cartilage with slips from the cricopharyngeus passing
dorsolaterally to
fuse posteriorly about 3 cm distal to the cricoid
cartilage. This results in a posterior triangular area devoid of longitudinal
muscle, Laimer triangle.
127
The longitudinal muscle of the esophagus also contracts during
peristalsis, with
the net effect of transiently shortening the structure
by 2 to 2.5 cm.
The esophagus is normally atonic and its intraluminal pressure
closely reflects pleural pressure, becoming negative during inspiration
128
(tLESRs) are an important mechanism
in GERD pathogenesis and are the most frequent mechanism
for reflux during periods of normal LES pressure (see Chapter
46). tLESRs are distinguishable from swallow-induced relaxation
in several ways: (1) they are prolonged (>10 seconds) and independent
of pharyngeal swallowing; (2) they are associated with
contraction of the distal esophageal longitudinal muscle, causing
esophageal shortening; (3) there is no synchronized esophageal
peristalsis; and (4) they are associated with crural diaphragm
inhibition, which is not the case with swallow-induced relaxation
(Fig. 44.7).27,28 tLESRs occur most frequently in the postprandial
state during gastric distention. In the setting of the completely
relaxed EGJ during tLESRs, even the minimal gastroesophageal
pressure gradients observed with gastric distention (3 to 4 mm
Hg) are sufficient to facilitate gas venting of the stomach. Thus,
tLESRs are the physiologic mechanism of belching.
129
Achalasia is the most easily recognized and best-defined motor
disorder of the esophagus
affecting both genders equally
| and usually presenting between 25 and 60 years of age
130
The most common structural abnormalities of the
| hypopharynx associated with dysphagia are
hypopharyngeal
| diverticula and cricopharyngeal bars.
131
Achalasia is characterized by impaired LES relaxation with
| swallowing and aperistalsis in the smooth muscle esophagus.
If there are premature, spastic contractions in the esophageal
body, the disease is referred to as spastic (type III) achalasia.
132
damage to the innervation
| of the smooth muscle segment of the esophagus
(including
the LES) with loss of ganglion cells within the myenteric
(Auerbach) plexus.
133
Muscle strips from the circular layer of the esophageal body of
achalasics contract when directly stimulated by ACh but fail to
respond to ganglionic stimulation by nicotine,
indicating a postganglionic
excitatory defect
Regardless of excitatory ganglion neuron impairment, it is clear
that inhibitory ganglion neuron dysfunction is as an early manifestation
of achalasia. These neurons mediate deglutitive inhibition
(including LES relaxation) and the sequenced propagation
of esophageal peristalsis; their absence offers a unifying hypothesis
for the key physiologic abnormalities of achalasia: impaired
LES relaxation and aperistalsis
Achalasics have been shown to
lack NO synthase and have a marked reduction of VIP-staining
neurons in the gastroesophageal junction.
134
The neuromuscular pathology responsible for DES is
| unknown and there are no known risk factors.
The most striking
reported pathologic change is of diffuse muscular hypertrophy or hyperplasia in the distal esophagus with thickening of up to 2 cm.
135
Chicago Classification labels this condition
| “jackhammer esophagus” when
2 such contractions occur in
| a manometric study
136
All patients have solid food dysphagia;
the majority of patients also have variable degrees of
liquid dysphagia.
Clinical manifestations of achalasia may include dysphagia,
regurgitation, chest pain, hiccups, halitosis, weight loss,
and aspiration pneumonia
achalasia
It tends to be nonbilious,
nonacid, and mixed with copious amounts of saliva.
neuromuscular apparatus facilitating UES relaxation
as part of the belch reflex is compromise
137
The major symptoms of DES are
dysphagia and chest pain.
Weight loss is rare
Dysphagia is usually intermittent and sometimes
related to swallowing specific substances such as red wine
or liquids at extreme hot or cold temperature
138
Pseudoachalasia becomes more likely
| than idiopathic achalasia with advanced age (>50 years),
abrupt
and recent onset of symptoms (<1 year), and early weight loss in
excess of 7 kg.
139
Dysphagia is common in the early period following fundoplication,
and patients are advised to consume soft diets for the first
2 to 4 postoperative weeks.
Dysphagia that persists longer than
4 weeks should be evaluated with an upper endoscopy or barium
esophagogram to assess the integrity of the wrap and evaluate
for possible paraesophageal hernia.
140
Features suggesting an esophageal, as opposed to a
cardiac, etiology of pain include: (1) prolonged nonexertional pain,
(2) pain that interrupts sleep, (3) meal-related pain, (4) relief with
antacids, and (5) additional accompanying esophageal symptoms
such as heartburn, dysphagia, or regurgitation.
141
should be the first test for evaluating newonset
dysphagia, because it combines the ability to detect most
structural causes of dysphagia with the ability to obtain biopsies.
Upper endoscopy
142
Achalasia
Type I: No contractility
Type II: >= 20% PEP
Type II: >= 20% Spasm (DL <4.5 sec)
In the patient with classic achalasia (Type I), there is no significant pressurization within
the body of the esophagus and EGJ relaxation is impaired;
swallow from a Type II patient, the “achalasia with compression” subtype, shows rapid pan-esophageal pressurization of the fluid column trapped between the sphincters as the esophagus shortens. The pressure topography plot in the
Type III patient is typical of spastic achalasia.
143
Type I (classic) 100% failed peristalsis, IRP > ULN
```
Type II (with esophageal
compression)
100% failed peristalsis and
panesophageal pressurization with
≥20% of swallows; mean IRP > ULN
```
Type III (spastic) No normal peristalsis, premature
contractions with ≥20% of swallows,
mean IRP > ULN
144
DES Mean IRP < ULN, ≥20% premature
contractions with DCI >450 mm
Hg•sec•cm, some normal peristalsis
may be present
```
Hypercontractile (jackhammer)
esophagus
At least 2 swallows with DCI >8000 mm
Hg•sec•cm, may involve or even
localize to the LES
Absent contractility Mean IRP ≤10 mm Hg, 100%
absent contractility (DCI <100 mm
Hg•sec•cm)
```
145
The major complication of pneumatic dilation is esophageal
perforation, with a reported incidence ranging between 0% and
5% and a global average of 1%.86
With most perforations readily
evident (or at least suspected) within an hour of the procedure
because of persistent or severe chest pain, fever, or subcutaneous
emphysema, patients should be observed for signs of an esophageal
leak for at least 2 hours after pneumatic dilation.
146
per oral endoscopic myotomy
| (POEM),
requires making a transverse mucosal incision in the
mid-esophagus, entering it, and creating a submucosal tunnel all
the way to the gastric cardia using a forward-viewing endoscope
with a transparent distal cap and a triangular dissection knife
Once the subcutaneous tunnel is complete, the endoscope is withdrawn
and selective myotomy of the circular muscle accomplished
with electrocautery tools for a variable length up the esophagus
and 2 cm distal to the EGJ onto the gastric cardia. Endoclips are
then used to seal the entry incision.
147
may develop in the achalasic esophagus.
Squamous cell carcinoma
148
Medications
directly damage the esophageal mucosa through 1 of 4 known
mechanisms:
(1) production of a caustic acidic solution (e.g.,
ascorbic acid and ferrous sulfate); (2) production of a caustic alkaline
solution (e.g., alendronate); (3) creation of a hyperosmolar
solution in contact with esophageal mucosa (e.g., potassium chloride);
and (4) direct drug toxicity to the esophageal mucosa (e.g.,
tetracycline).
149
diffuse
| sloughing appearance of the mucosa, also known as
esophageal dissecans
| superficialis,
150
particularly for gelatin capsules and larger tablets,3
| the following recommendations are made:
(1) medications should
be swallowed with at least 8 ounces of a clear liquid; (2) patients
should remain upright for at least 30 minutes following ingestion
of the medication; and (3) in patients with potential underlying
increased risk for pill-induced injury (e.g., inability to follow the
previous instructions, poor esophageal motility, anatomic compromise
of the esophageal lumen), one should search for alternative
safer medications or carefully weigh the risks and benefits of
this medication against the disease for which this medication is
necessary.
151
has low potential for causing esophageal
injury, if at all.42 Part of this might be explained by the rapid
esophageal transit and subsequently minimal contact time of
the drug with esophageal mucosa
Risedronate
152
Chemotherapy given months after thoracic irradiation
| to the esophagus, particularly doxorubicin, may cause a
“recall”
esophagitis.
Vinca alkaloid drugs are neurotoxic, and dysphagia
may complicate vincristine therapy.82 Crizotinib, a tyrosinekinase
inhibitor used for non–small cell lung cancer, has been
reported to cause severe ulcerative esophagitis similar to a more
typical pill-induced esophagitis
153
The only agent that has been shown effective in preventing
postsclerotherapy strictures and in healing ulcers is sucralfate,
either alone or in combination with antacids and cimetidine.102,103
Acid suppressive therapy alone, with either H2RAs or PPIs, has
not been shown to be effective in preventing or healing postsclerotherapy
ulcers or strictures.
154
lacerations of the gastric cardia
due to forceful vomiting.140 The laceration is felt to result from
shearing forces on the gastroesophageal junction and proximal
stomach as it herniates through the diaphragm because of high
intra-abdominal pressures due to forceful vomiting.
Mallory-Weiss syndrome
this shearing force has its greatest
effect when there is a hiatal hernia, thereby exposing a relatively
large-volume dilated sac to a high wall tension.
most tears will occur
within 2 cm of the gastroesophageal junction, the likelihood
of a more distal tear in the proximal portion of the stomach is
increased when a larger hiatal hernia is present
155
MW tear
Typically, one laceration is seen
at the time of endoscopy, most commonly along the lesser curve
of the cardia, although more than one tear may occur in up to
10% of patients.14
3 Bleeding is typically self-limited, but may be
| massive in up to 10% of patients
156
A more extreme version of an esophageal tear that occurs from
an acute increase in intra-abdominal pressure and accentuation of
the intragastric-to-intrathoracic pressure gradient is Boerhaave
syndrome
In this syndrome, a transmural tear with perforation
occurs.
The perforation specifically occurs at the margin of the
contact between “clasp” and oblique esophageal fibers
The clinical presentation is often catastrophic, with shock and
sepsis due to a large esophageal perforation. Not surprisingly, death
occurs in up to a third of patients.170 Because of the acute presentation
of severe chest pain, it is often confused with acute cardiac or
pulmonary events, dissecting aortic aneurysm, or pancreatitis
157
booerhave
Diagnosis is suggested by subcutaneous emphysema
with crepitus and radiographic findings of pneumomediastinum
and a left pleural effusion (that may contain salivary amylase, erroneously
suggesting pancreatitis) or even a frank empyema. Perforation
of the esophagus may be confirmed by esophageal contrast
studies using Gastrografin.
158
is a rare entity in which an
abrupt bleed occurs between the mucosa and muscularis propria of
the esophageal wall, often for a long length of the esophagus.
Spontaneous esophageal hematoma
159
One third of patients classically present with
a triad of retrosternal chest pain, dysphagia, and hematemesis and
50% present with at least 2 of these symptoms
Spontaneous esophageal hematoma
Diagnosis can be made by several means. CT of the chest
demonstrates a diffusely thickened esophagus and sometimes a
“double barrel” appearance with obliteration of the esophageal
lumen.
Endoscopically, obliteration of the esophageal lumen is
seen with visualization of a long, deep, friable, blue submucosal
mass with or without a visible tear
160
HSV esophagitis
may be diagnosed by several methods. These include (1) characteristic
viral cytopathic effect and/or demonstration of viral particles
by electron microscopy on esophageal brushing or biopsy;
(2) isolation by culture of HSV from mucosal biopsies; (3) HSV
DNA detection in esophageal tissue by PCR; (4) demonstration
of HSV through techniques of immunohistochemistry in esophageal
tissue; and (5) isolation of HSV from oropharyngeal secretions
in the setting of stomatitis and multiple esophageal ulcers
hsv
Histologic stains of HSV-infected epithelial cells demonstrate
multinucleated giant cells, ballooning degeneration, “ground
glass” intranuclear Cowdry type A inclusion bodies, and margination
of chromatin
161
transmitted. Esophageal infections
with HPV are typically asymptomatic. HPV lesions are most
frequently found in the
mid- to distal esophagus as erythematous
macules, white plaques, nodules, or exuberant frond-like lesions The diagnosis is made by histologic demonstration of koilocytosis
(an atypical nucleus surrounded by a ring), giant cells, or
by immunohistochemical stains
Treatment is often not necessary,
although large lesions have required endoscopic removal. Other
treatments such as those using systemic interferon (IFN)-α, bleomycin,
and etoposide have yielded varying results
162
Acute esophageal necrosis (black esophagus) is a rare poorly
understood disorder. Ischemia and impaired mucosal barrier are
thought to play a role in its pathogenesis,241 though other etiologies
suggested have included
severe reflux and CMV.242 Settings
in which black esophagus have been described include diabetes
mellitus, hematologic and solid organ malignancy, malnutrition,
renal insufficiency, cardiovascular compromise, trauma, and
hypercoagulation.
163
There is no clear association between gender and peptic stricture,5
but
men are at a greater risk of esophagitis, Barrett’s esophagus,
and adenocarcinoma than women.
Obesity is a major risk factor for GERD symptoms (odds ratio
1.73), erosive esophagitis (odds ratio 1.59), Barrett’s esophagus
(odds ratio, 1.24), and esophageal adenocarcinoma (odds ratio
2.45)
Central obesity, as measured by the waist-to-hip ratio,
may be more important than BMI in association with complicated
GERD
164
Certain forms of physical activity may increase
GER symptoms in susceptible individuals, such as stooped posture,
bicycle riding, weight lifting, and swimming.21 On the other
hand, moderate, regular aerobic exercise has been inversely associated
with GERD symptoms
Tobacco use is weakly associated
with GERD symptoms in cross-sectional studies (summary odd
ratio, 1.26).3 This relationship is supported by an 18-year longitudinal
study in which decreased tobacco smoking was associated
with a 3-fold decrease in GERD symptoms when compared
with individuals who continued to smoke tobacco
alcohol use was not strongly associated with
GERD symptoms, (summary odds ratio, 1.11).3 Although patients
often report worse symptoms after red wine than white (perhaps
related to the tannins in red wine), a randomized trial found that
red wine had less effect on LES pressure and acid reflux than white
wine.
165
Tobacco is an important risk factor for erosive esophagitis
| and esophageal adenocarcinoma,
but there is no relationship
| between alcohol and erosive esophagitis or Barrett’s esophagus
166
The first tier of the 3-tiered esophageal defense against acid damage,
the antireflux barriers, is an anatomically complex region including the intrinsic LES, diaphragmatic crura, intra-abdominal location of the LES, the phrenoesophageal ligaments, and the acute angle of His
The LES involves the distal 3 to 4 cm of the esophagus and
at rest is tonically contracted
167
Increase LES Pressure
Gastrin
Motilin
Substance P
α-Adrenergic agonists
β-Adrenergic antagonists
Cholinergic agonists
Protein
```
Antacids
Baclofen
Cisapride
Domperidone
Histamine
Metoclopramide
Prostaglandin F2α
```
Decrease LES Pressure
```
CCK
Secretin
Somatostatin
Vasoactive intestinal
peptide
```
α-Adrenergic antagonists
β-Adrenergic agonists
Cholinergic antagonists
Chocolate
Fat
Peppermint
```
Barbiturates
Calcium channel blockers
Diazepam
Dopamine
Meperidine
Morphine
Prostaglandins E2 and I2
Serotonin
Theophylline
```
168
The proximal portion of the LES is normally 1.5 to 2
| cm above the squamocolumnar junction,
whereas the distal segment,
about 2 cm in length, lies within the abdominal cavity.
This location maintains gastroesophageal
competence during intra-abdominal pressure excursions. Resting
LES pressure ranges from 10 to 30 mm Hg, with a generous
reserve capacity because only a pressure of 5 to 10 mm Hg is
necessary to prevent GER
During deep inspirations and some periods of increased abdominal
straining, these changes may lead to pressures of 50 to 150
mm Hg.
169
Reflux usually occurs via 4 mechanisms:
tLESR, low LES pressure,
swallow-associated LES relaxation, and straining during
periods of low LES pressure
170
tLESRs are the most frequent mechanism for reflux in patients
with healthy sphincter pressures (Fig. 46.2)
. tLESRs occur independently
of swallowing, are not accompanied by esophageal
peristalsis, persist longer (>10 seconds) than swallow-induced
LESRs, and are accompanied by inhibition of the crural diaphragm.
Possible factors
determining whether reflux occurs include abdominal straining,
presence of a hiatal hernia, degree of esophageal shortening,
and duration of tLESRs.
The dominant stimulus for a tLESR is
distention of the proximal stomach by either food or gas,
171
The dominant stimulus for tLESRs is distension of the proximal
stomach,
which activates mechanoreceptors in the intraganglionic
| lamellar endings of vagal afferents
172
Strained-Induced or Free Reflux
Free reflux is characterized
by a fall in intraesophageal pH without an identifiable change
in intragastric pressure, usually occurring when LES pressure is
less than 5 mm Hg. Reflux due to a low or absent LES pressure is
uncommon, usually observed in patients with end-stage scleroderma
or after myotomy for achalasia
This type of reflux is unlikely when the LES pressure is greater than
10 mm Hg and there is no hiatal hernia
173
requires 2 “hits” to
the EGJ.42 Patients with a normal EGJ require inhibition of the
LES and crural diaphragm for reflux to occur (i.e., tLESRs).
In
contrast, when a hiatal hernia is present compromising the function
of the crural sphincter, reflux can occur with only relaxation
of the LES, during periods of LES hypotension, swallowinginduced
relaxation, and straining.
174
hiatal hernia promotes reflux through several mechanisms
(Fig. 46.4). Proximal displacement of the LES from the crural diaphragm
into the chest reduces basal LES pressure and shortens
the length of the high-pressure zone; this is primarily due to loss
of the intra-abdominal LES segment.50
Hiatal hernia eliminates
the increase of LES pressure that occurs during straining and
increases tLESR frequency during gastric distention with gas.56,57
Hiatal hernias serve as a persistent vestibule for gastric acid (the
so-called acid pocket
Hiatal hernias that are large (≥3 cm) and nonreducible
(hernias in which the gastric rugal folds remain above
the diaphragm between swallows) are especially prone to reflux.
175
Gastric pH is usually around 2 in the fasting state.
During meals,
and for approximately 90 minutes thereafter, the pH remains elevated owing to the buffering effects of the food. Herein lies a
paradox because most episodes of acid reflux occur immediately after a meal.
This paradox is explained by the identification of a
zone in the gastric cardia that remains unbuffered, now referred
to as the acid pocket
In GERD patients with hiatal hernia, the acid
pocket is further enlarged because of the proximal migration of
the LES.
176
In addition, when the acid pocket is located about the
diaphragm, especially in a hiatal hernia, more than 70% of the
tLESRs were accompanied by acid reflux.
In contrast, less than
20% of tLESRs were accompanied by acid reflux when the acid
pocket was below the diaphragm.
177
The second tier of protection against reflux damage is esophageal
acid clearance
Primary peristalsis is elicited by swallowing.
Secondary peristalsis, initiated by esophageal distention from
acid reflux, is much less effective in clearing the refluxate, thus
offering only an ancillary protective role
178
Peristaltic dysfunction (i.e., failed peristaltic contractions,
hypotensive or weak [<30 mm Hg] peristaltic contractions that
incompletely empty the esophagus) increases in frequency with
the severity of esophagitis
Saliva is the second essential factor required for normal esophageal
acid clearance. The stimulus for salivation appears to be the
presence of acid in the proximal esophagus (20 cm above LES).68
The normal daily volume of saliva is 1.2 L, which may triple in
response to persistent esophageal acidification. Saliva is a weak base with a pH of
6.4 to 7.8.
179
Cigarette smoking promotes GER. Originally
attributed to nicotine’s effect on lowering LES pressure,
cigarette smokers also have hyposalivation, leading to prolonged
esophageal acid clearance times
third tier for esophageal defense known as tissue
resistance. Conceptually, tissue resistance can be subdivided into
pre-epithelial, epithelial, and postepithelial factors,
180
The pre-epithelial defense in the esophagus is poorly developed.
There is neither a well-defined mucous layer nor buffering
capacity by the surface cells to secrete bicarbonate ions into
the unstirred water layer
The epithelial defenses consist of structural and functional components.
Structural components include the cell membranes and
intercellular junctional complexes of the esophageal mucosa. This
structure is a 25- to 30-cell-thick layer of nonkeratinized squamous
epithelium
181
dilated intercellular spaces are the earliest
| markers of esophageal epithelial cellular damage
The postepithelial defense is provided by the esophageal blood
supply.
182
Heartburn is the classic symptom of GERD, with patients generally
reporting a burning feeling rising from the stomach or lower
chest and radiating toward the neck, throat, and occasionally the
back.101
It usually occurs postprandially, particularly after large
meals or after ingesting spicy foods, citrus products, fats, chocolates,
and alcohol.
The supine position and bending over may
exacerbate heartburn. Sleep deprivation as well as psychological
or auditory stress may lower the threshold for symptom perception
183
GERD is usually diagnosed symptomatically by the occurrence
of heartburn 2 or more days a week, although less frequent symptoms
do not preclude the disease
The receptor that mediates the sensation of heartburn during
acid perfusion has not been identified, although the capsaicin
receptor, or vanilloid receptor 1 (TRPV1), is a leading candidate.
184
Water brash is the sudden appearance in the mouth of a slightly
sour or salty fluid. It is not regurgitated fluid, but rather secretions
from the salivary glands in response to acid reflux
The most common is pregnancy, in which 30% to 80% of women
complain of heartburn, especially in the first trimester (see
Chapter 40). Pregnancy increases the risk for reflux by reducing
LES pressure due to the effects of estrogen and progesterone and
possibly mechanical factors from the gravid uterus.
185
Up to 90%
of patients with scleroderma (PSS or CREST syndrome) have
GERD due to smooth muscle fibrosis causing low LES pressure
and weak or absent peristalsis
An empirical trial of acid suppression is the simplest method for
diagnosing GERD and assessing its relationship to symptoms.
186
Symptoms usually respond to a PPI trial in 1 to
2 weeks. If symptoms disappear with therapy and then return
when the medication is discontinued, GERD has been established.
In empirical trials for heartburn, the initial PPI dose was
high (e.g., omeprazole 40 to 80 mg/day), usually given for at
least 2 weeks, and a positive response was defined as at least
50% improvement in heartburn. Using this approach, the PPI
empirical trial has a sensitivity of 68% to 83% but poor specificity
for determining the presence of GERD.
187
The earliest endoscopic signs of acid reflux include edema and
erythema, but these findings are nonspecific and dependent on
the quality of endoscopic visual images.151 More reliable signs
are friability, granularity, and red streaks.
Friability (easy bleeding)
results from the development of enlarged capillaries near the
mucosal surface in response to acid. Red streaks extend upward
from the esophageal junction along the ridges of the esophageal
folds.152 Erosions develop with progressive acid injury, characterized
by a shallow break in the mucosa with a white or yellow
exudate surrounded by erythema
188
Most patients with GERD are treated initially with PPIs and
| without endoscopy.
The important exception is the patient experiencing
“alarm” symptoms: dysphagia, odynophagia, weight loss,
vomiting, and GI bleeding
189
Other indications include typical GERD
symptoms that persist despite a 4- to 8-week trial of twice-daily
PPI therapy,
and patients with severe esophagitis after a 2-month
| PPI course,
190
Classic changes of basal cell hyperplasia and increased
height of the rete peg, both representing increased epithelial
turnover of the squamous mucosa, are sensitive but not specific
histologic findings for GERD
Acute inflammation characterized
by the presence of neutrophils and often eosinophils
(Fig. 46.8) is very specific for esophagitis;
191
Los Angeles Endoscopic Classification System for
| Esophagitis
Grade A One or more mucosal breaks confined to folds, ≤5 mm
Grade B One or more mucosal breaks >5 mm confined to folds but not continuous between the tops of mucosal folds
Grade C Mucosal breaks continuous between tops of 2 or more mucosal folds but not circumferential (<75%)
Grade D Circumferential mucosal break
(at least 75%)
192
GERD exists as a spectrum of disease
| severity or as a categorical disease in 3 distinct groups:
erosive,
| nonerosive, and Barrett’s esophagus
193
Esophageal pH testing identifies 3 distinct subsets of nonerosive
GERD patients.
First are the patients with excessive acid reflux
who usually respond to PPI therapy.
Second are the patients with normal acid reflux parameters but a good correlation between
their symptoms and acid reflux episodes. This group represents 30% to 50% of nonerosive GERD patients and, based on recent Rome IV criteria, is classified as “reflux hypersensitivity.”
These patients probably have heightened esophageal sensitivity
to acid and are less likely to respond to antireflux therapy
The third group is characterized by normal acid exposure times and poor symptom correlation. This group is classified as “functional
heartburn.
194
Patients with erosive esophagitis tend to be male, older, and
overweight and are more likely to have hiatal hernias
85% of patients with
erosive GERD and given no maintenance reflux therapy will
relapse within 6 months of stopping PPI therapy
195
The most common fatal causes are hemorrhagic esophagitis,
aspiration pneumonia, ulcer perforation, and rupture with
severe esophagitis
Strictures occur in 7% to 23% of patients with untreated reflux
esophagitis. They are commonly seen in older men194 and linked
to chronic NSAID use.195 Stricture formation is complex, starting
as reversible inflammation with edema, cellular infiltration,
and vascular congestion, progressing to collagen deposition, and
ending in irreversible fibrosis
196
Peptic strictures are smooth-walled, tapered, circumferential
narrowings in the lower esophagus, usually less than 1
cm long but occasionally extend to 8 cm
today a Schatzki’s ring is considered a forme
fruste of an early peptic stricture.196 All stricture patients
should undergo endoscopy to confirm the benign nature of the
lesion and take biopsies to exclude EoE, cancer, and Barrett’s
esophagus.
197
Antacids increase
| LES pressure but work primarily by buffering gastric acid, albeit
Gaviscon, containing alginic acid and antacids, mixes
with saliva to form a highly viscous solution that floats on the
gastric pool, acting as a mechanical barrier. Recent studies found
that the raft colocalized with the postprandial acid pocket and
displaced it below the diaphragm, resulting in significant suppression
of postprandial acid reflux.
198
Currently, the only medication available that decreases
| tLESRs is
baclofen, a GABAB agonist used for many years to
treat spasticity. Baclofen (5 to 20 mg 3 times daily) significantly
reduces tLESRs, decreases both acid and duodenal reflux, and
improves symptoms in GERD patients treated for 4 weeks to several
months Side effects including drowsiness, dizziness, nausea, and vomiting
require discontinuation in up to 20% of patients
Other
GABAB agonists with improved tolerability have been developed
(lesogaberan, arbaclofen placarbil) but were abandoned mainly
because of limited clinical efficacy
199
These drugs (cimetidine, ranitidine, famotidine, and nizatidine)
are more effective in controlling nocturnal than meal-stimulated
acid secretion
The 4 H2RAs are equally effective when used in
proper doses, usually twice a day before meals. GERD trials
H2RAs given at bedtime successfully
eliminated this problem in a study, suggesting a new indication
for H2RAs in the PPI era
200
PPIs inhibit meal-stimulated and nocturnal acid secretion to
a significantly greater degree than H2RAs but rarely render
patients achlorhydric.
PPIs should be taken before the first meal of the day, when most
proton pumps become active. Because not all pumps are active
at any given time, a single PPI dose will not inhibit all pumps. A
second dose, if necessary, can be taken before the evening meal;
however, this is an off-label indication. PPIs do not “cure” reflux
disease, rather they treat GERD in an indirect way by decreasing
the number of acid reflux episodes. In exchange, the weakly acidic
(pH > 4) episodes are increased, while the total number of reflux
episodes and proximal extent are not affected by PPI therapy
201
PPIs (omeprazole, lansoprazole, rabeprazole, pantoprazole,
and esomeprazole) have superior efficacy compared with
H2RAs on the basis of their ability to maintain an
intragastric
pH greater than 4 from 10 to 14 hours daily compared with
approximately 6 to 8 hours daily with the H2RAs
PPIs
are superior to H2RAs in completely relieving heartburn symptoms
in patients with severe GERD, usually within 1 to 2 weeks
202
PPIs are well tolerated, with headaches and diarrhea being the
most common side effects. Fasting serum gastrin levels increase
with all the PPIs, but the elevations generally do not exceed the
normal range and return to baseline values within 1 to 4 weeks
of drug discontinuation.
Omeprazole decreases the clearance of
diazepam, warfarin, and clopidogrel owing to competition for the
cytochrome P450 isoenzyme P2C19.
203
After esophagitis is healed, recurrence
within 6 months of stopping medication occurs in more than
80% of patients with severe esophagitis and in 15% to 30% of
those with milder esophagitis
Fundic gland polyps are the most common gastric polyp found
at endoscopy
Chronic use of PPIs is purported to affect the absorption of calcium,
vitamin B12, magnesium, and iron.
increased risk of enteric infections (Salmonella, Campylobacter,
and Clostridioides difficile) and of spontaneous bacterial
peritonitis253,254 with acid suppression
204
performed laparoscopically through the abdomen, are
| the
Nissen 360-degree fundoplication and the Toupet partial
| fundoplication
205
Barrett esophagus is diagnosed by endoscopic examination, and
2 criteria must be fulfilled.
First, the endoscopist must ascertain
that columnar epithelium lines 1 cm or greater of the distal esophagus.
Second, biopsy specimens of that columnar epithelium
must show evidence of metaplasia, which is a change from one adult tissue type to another. To ascertain that columnar epithelium lines the distal esophagus, the endoscopist first must locate the esophagogastric junction (EGJ), which is recognized as the most proximal extent of the gastric folds, and then determine
that columnar epithelium extends 1 cm or greater above the EGJ into the esophagus
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
206
Barrett esophagus can be further categorized as long segment
(when the metaplastic epithelium extends at least 3 cm above the
EGJ) or short segment (when <3 cm of metaplastic epithelium
lines the distal esophagus).6
Short-segment Barrett esophagus,
| which is by far the most common form of the disease
207
Barrett esophagus typically is discovered during endoscopic
examinations performed for the evaluation of GERD symptoms
in middle-aged and older adults
The average age at the time
of diagnosis is approximately 55 years
White men predominate in most
series, and, for unknown reasons, Barrett esophagus is uncommon
in black and Asian populations
208
cigarette smoking
and alcohol consumption are very strong risk factors for squamous
cell carcinoma of the esophagus, cigarette smoking only
modestly increases the risk for esophageal adenocarcinoma and
alcohol does not appear to affect that risk at all.
Metaplastic Barrett cells first acquire
| mutations leading to inactivation of p53.
209
To find dysplasia in Barrett esophagus,
endoscopists traditionally have used the “Seattle biopsy protocol,”
a random biopsy sampling system in which 4-quadrant biopsies
are taken at 1- to 2-cm intervals throughout the length of Barrett
metaplasia.
latest guideline on the
management of Barrett esophagus by the ACG recommends
that Barrett patients should receive once-daily PPI therapy for
chemoprevention
210
Medical societies currently
do not recommend the routine prescription of aspirin or other
NSAIDs for chemoprevention in patients with Barrett esophagus,
because it is not clear that the potential benefits of NSAIDs
outweigh their risks of serious GI and cardiovascular side effects
of endoscopic screening for Barrett esophagus only for patients
who have multiple risk factors for esophageal adenocarcinoma,
including chronic GERD, age 50 years or older, male gender,
white race, hiatal hernia, intra-abdominal body fat distribution
(central obesity), smoking history, and history of Barrett esophagus
or adenocarcinoma in a first-degree relative
211
2 general types of endoscopic therapies available for the
treatment of Barrett esophagus: (1) endoscopic ablative therapy,
which uses heat (delivered by laser, electrocoagulation, argon
plasma coagulation [Video 47.1], or radiofrequency energy),
cold (cryotherapy, delivered by spraying cold carbon dioxide or
nitrous oxide gas), or photochemical energy (photodynamic therapy
[PDT]) to destroy the Barrett epithelium; and
(2) endoscopic
resection including EMR (Video 47.2) and endoscopic submucosal
dissection, in which a diathermic snare or endoscopic knife is
used to remove a large segment of Barrett mucosa with submucosa.
After these endoscopic treatments, patients are treated with PPIs
212
RFA is now widely regarded as the procedure of choice
for ablating Barrett esophagus with dysplasia, both high grade
and low grade
Because of the high risk for lymph node metastases when
Barrett neoplasms involve the submucosa, accurate T-staging
of tumors is crucial to determine whether endoscopic therapy is
feasible. EUS had been considered the most accurate diagnostic
modality for T-staging, but a number of studies have shown
that EUS has very limited accuracy for T-staging early neoplasia
in Barrett esophagus
213
nodular lesions and other
visible irregularities in Barrett esophagus should be removed by
EMR for T-staging prior to performing endoscopic ablation.
If the EMR specimen shows submucosal invasion, then further
endoscopic therapy is not advised.
EET now is widely regarded as the procedure of choice for treating
mucosal neoplasia in Barrett esophagus, including low-grade
dysplasia, high-grade dysplasia, and intramucosal carcinoma.
EET generally is not recommended when EMR reveals submucosal
invasion, because of the high frequency of lymph node
metastases in this situation
214
Recurrences of Barrett metaplasia and dysplasia are most frequent
in the first year after achieving CE-IM by EET
Patients with Barrett esophagus should be treated with PPIs
in whatever dose is necessary to control GERD symptoms and
eliminate endoscopic signs of reflux esophagitis.
Asymptomatic
patients without reflux esophagitis can be treated with
once-daily PPI therapy for chemoprevention
215
nondysplastic Barrett esophagus, the risks
and benefits of endoscopic surveillance should be presented
in detailed discussion. Those who opt for surveillance should
have it performed at intervals of every 3 to 5 years.
appear irregular or suspicious for neoplasia, the
endoscopists should take targeted biopsies or, preferably,
the suspicious area should be removed by EMR. In addition
to these targeted specimens, the endoscopist should take
4-quadrant biopsy specimens every 2 cm throughout the
length of the Barrett metaplasia. In patients already known
to have dysplasia, 4-quadrant biopsy specimens should instead
be taken every 1 cm throughout the length of the Barrett
metaplasia.
216
“indefinite for dysplasia,” PPI therapy
should be optimized and endoscopy repeated in approximately
8 weeks, with biopsy specimens taken at 1-cm intervals. If the
diagnosis of indefinite for dysplasia persists, management options
include surveillance endoscopy every 12 months or referral
to a center with special expertise in managing Barrett
esophagus.
After achieving CE-IM for patients with high-grade dysplasia
or intramucosal carcinoma in Barrett esophagus, endoscopic
surveillance is performed every 3 months for the
first year, every 6 months in the second year, and annually
thereafter.
After achieving CE-IM for patients with low-grade dysplasia,
endoscopic surveillance is performed every 6 months for the
first year, and annually thereafter
217
ESCC is the most common form of esophageal cancer worldwide
In industrialized countries, the 2 most important risk factors
are tobacco use and excess alcohol consumption (Box 48.1).16-19
Furthermore, these 2 independent risk factors have a synergistic
effect on cancer incidence
The risk of developing ESCC
with active tobacco smoking increases 3- to 9-fold the highest risk has been reported with smoking cigarettes
Alcohol
use has been reported to have a slightly lower risk compared
to tobacco, increasing risk of ESCC by 3- to 5-fold
218
The risk
increases significantly with alcohol intake above the maximum
recommended U.S. dietary guidelines of 140 g/week.1 Acetaldehyde,
the first metabolite of ethanol metabolism, is a class I
carcinogen.
Zinc deficiency is thought to potentiate
the carcinogenic effect of nitrosamines. Selenium supplementation
is also thought to have chemo-preventive effects against
ESCC. After a 10-year follow-up, a study showed that selenium
supplements (along with β-carotene and vitamin E) reduced risk
of esophageal cancer death by 17% among participants younger
than 55 years old.
219
```
ESCC
Tobacco
Alcoholic beverages
Low consumption of fruits and vegetables
Low socioeconomic status
Micronutrient deficiencies
High-temperature foods
Achalasia
Lye ingestionw
Rare disorders (Plummer-Vinson syndrome, Fanconi anemia,
and tylosis)
```
EAC
Tobacco
GERD
Obesity
220
fact, a large achalasia cohort from
Sweden was shown to have an increased risk for both ESCC and
EAC.46 The mechanism is likely due to stasis of food material
in the esophagus, leading to chronic inflammation
EAC is the second most common form of esophageal carcinoma
| worldwide
221
The anatomic distribution
of esophageal cancer has shifted from the upper third
of the esophagus to the lower third. The lower third of the
esophagus, the location where adenocarcinoma usually arises,
was the only esophageal location with an increased incidence.
GERD is the most important risk factor for the development
| of EAC
222
BE is the
only identifiable premalignant condition for EAC and is defined
by the replacement of the normal stratified squamous epithelium
with a columnar-lined distal esophagus with intestinal metaplasia
EAC, there is a gradual accumulation of somatic-cell genetic
abnormalities that occur during the metaplasia-dysplasia-carcinoma
sequence in the esophageal epithelium
223
ESCC, on the other hand, is thought to arise from
hyperproliferative epithelium that progresses to low-, intermediate-,
and high-grade dysplasia (HGD) leading, ultimately, to invasive
cancer
HER2/
neu) is a prognostic factor in esophageal cancer.116-118 HER2/
neu gene amplification correlates with shortened patient survival
and independently predicts poor outcomes in patients
with EAC
Expression of the tumor-suppressor gene
TP53 in ESCC is an independent prognostic factor. Tumors
with low p53 staining are associated with significantly longer
survival than tumors with high p53 protein expression
224
ESCC, expression of cyclin D1, a key cell cycle regulator (see
Chapter 1), has been associated with shorter patient survival
compared to cyclin D1-negative patients
p21 staining in ESCC has been associated with an improved
survival,126,127 and ESCC patients whose tumors had
high levels of p16 had longer survival
225
Survivin,
another member of the inhibitor of apoptosis gene family,
has been found to be a useful predictive factor in neoadjuvant
therapy for esophageal cancer. Specifically, partial responders
to neoadjuvant chemotherapy have lower survivin expression
than nonresponders.
High expression of VEGF is an independent, negative
prognostic factor in ESCC, although a correlation in EAC has
not been demonstrated.136 COX-2 is known to increase progressively
as the tissue progresses through Barrett metaplasia,
to dysplasia, and to frank EAC.132 In ESCC, COX-2 overexpression
correlates with depth of tumor invasion, tumor stage,
and reduced survival
Amplification of fibroblast growth
factor receptor 1 was shown to be an independent adverse
prognostic factor in ESCC.138
226
EAC and ESCC have a similar clinical presentation
despite the differences in demographics and risk factors.
progressive dysphagia and weight loss are the
most common symptoms
Odynophagia is a
less common symptom and usually indicates the presence of an
ulcerated lesion.
227
anemia (iron
deficiency or chronic disease type), hypoalbuminemia, and/or
hypercalcemia (usually associated with osteolytic metastasis).
Although paraneoplastic syndromes are rare with esophageal cancer,
ESCC rarely can cause hypercalcemia due to tumoral production
of a circulating parathyroid hormone-related protein
The diagnosis of esophageal cancer is primarily made by
endoscopic biopsies in a patient presenting with progressive
dysphagia to solids (Fig. 48.2). The endoscopic appearance is
similar between advanced ESCC and EAC; however, approximately
three quarters of all EAC lesions are found in the distal
esophagus whereas ESCC is more frequent in the proximal to
middle esophagus
228
It is critical for endoscopists to spend adequate
time inspecting the esophagus and document landmarks such as
the gastroesophageal junction, extent of BE using the Prague C
(circumferential) and M (maximal extent) criteria, the presence
or absence of extension into the stomach, and the exact location
of the tumor
Conventional chromoendoscopy involves the use of special stains
to highlight subtle architectural changes to help direct biopsies
and predict histology. Lugol’s iodine, methylene blue, acetic acid,
crystal violet, and indigo carmine are the most commonly used
stains.
229
Lugol’s iodine solution consists of a 0.5% to 3.0%
aqueous solution of potassium iodide. Iodine stains glycogencontaining
cells of the normal esophageal epithelium and is not
taken up by dysplastic or malignant cells that are glycogen depleted
(“pink color sign”).
Chromoendoscopy with Lugol’s iodine staining
has become the standard of care for screening of ESCC in
high-risk populations and has been shown to have a high sensitivity
rate of 89% to 100% with highly variable specificity rates due to
false positive lesions
230
In contrast, methylene blue, acetic acid,
and indigo carmine staining are more useful in the detection of
glandular abnormalities, as seen in EAC. These stains are sprayed
in the esophagus with the intent of improving characterization of
the mucosa resulting in selective uptake (vital staining—methylene
blue) or enhancement of mucosal surface pattern (contrast staining—
indigo carmine, acetic acid
Optical chromoendoscopy is another modality to detect signs of
dysplasia and cancer by using selective light filters to highlight
subtle architectural and vascular changes in the mucosa.
231
NBI is an imaging technique that is based on
| the optical phenomenon that the depth of light penetration into
NBI is the most
widely studied electronic chromoendoscopy technique to predict
histology during surveillance, improve detection of dysplasia, and
guide endoscopic eradication therapies.
232
AFI involves a technique that uses short-wavelength blue or
ultraviolet light to stimulate biological fluorophores (e.g., collagen,
porphyrins, flavins, aromatic amino acids) in the esophagus
CLE allows real-time, in vivo microscopic imaging of the
esophageal mucosa. It involves IV administration of a fluorescent
dye (most commonly fluorescein sodium) that is taken up by normal
mucosal cells. Fluorescent dye uptake is not seen in dysplastic
cells, and thus they appear dark
233
Optical coherence tomography emits near-infrared light to provide
cross-sectional images of tissue, which also has the potential
advantage of identifying submucosal lesions
Cost-benefit studies have been carried out to assess esophageal
cancer screening strategies.170 One study found that a strategy
of 1-time screening at age 50 would be the best approach
in underdeveloped high-risk areas, whereas a 3-time screening
strategy starting at age 40 (10-year intervals) would be preferable
in areas with better health care resources
234
1. One-time Lugol’s chromoendoscopy for high-risk Asian and
African populations beginning at the age of 40.
2. Endoscopy with Lugol’s or NBI every 6 months to 1 year after
completion of therapy for head and neck squamous cell cancer,
for 10 years.
3. Screening could also be considered for patients at high risk
(tylosis, achalasia, and caustic injury).
T1cancer that invades the lamina propria, muscularis mucosae, or submucosa and is subcategorized into
T1a (cancer that invades the lamina propria or muscularis mucosae)
T1b (cancer that invades the submucosa);
T2 cancer that invades the muscularis propria
T3 cancer that invades the adventitia;
T4 cancer that invades the local structures, and
is subcategorized as
T4a (cancer that invades adjacent structures such as the pleura, pericardium, azygos vein, diaphragm, or peritoneum) and
T4b (cancer that invades the major adjacent structures, such as the aorta, vertebral body, or trachea).
N1 (regional lymph node metastases involving 1 or 2 nodes), N2 (regional lymph node metastases involving 3 to 6 nodes), and
N3 (regional lymph node metastases involving 7 or more nodes
235
esophagogastric
junction such that cancers involving it with epicenters no more than 2 cm into the gastric cardia are staged as EAC and those with >2 cm involvement of the gastric cardia are staged as
gastric cancers.
Further classification for
T1a includes M1 (intraepithelial cancer),
M2 (invasion into the lamina propria), and
M3 (invasion to the muscularis mucosa).
T1b lesions also can be subdivided into SM1 (invasion into the upper third of the submucosa), SM2 (invasion into the middle third), and SM3 (invasion into the lower
third).
Tis and T1a lesions have a predicted lymph node metastasis rate up to 8% compared to T1b lesions, which have up to a 56% lymph node metastasis rate
236
The risk of lymph node involvement is related to several
factors (in decreasing order of frequency): grade III histology,
SM3 invasion, lymphatic invasion, vascular invasion, SM2 invasion,
and SM1 invasion
In ESCC, the best predictors of lymph
node invasion are SM3 invasion and vascular invasion, whereas in
EAC, the most important predictor is lymphatic invasion
237
determine the histologic type (ESCC or EAC) and the
histologic grade (degree of differentiation).189 The sensitivity for
mucosal biopsies reaches 96% when multiple biopsies are taken
(typically 6 to 8)
EUS is increasingly used to assess the depth of tumor invasion and
to distinguish T1 lesions from deeper infiltration. This distinction
helps to choose candidates for stage-appropriate therapies. EUS
is the only imaging modality that can clearly delineate the different
esophageal wall layers. It is considered by most experts to
be the best staging modality for T stage and locoregional lymph
node (N) staging (
238
Endosonographic features of
malignant lymph nodes include lesions that are hypoechoic with a
rounded and smooth surface, lesions >10 mm, and lesions located
in close proximity to the tumor
Surgery is the standard treatment for a medically optimized surgical candidate with a localized, non-superficial tumor.
For a patient with a localized tumor who is not a surgical candidate, definitive chemoradiation with curative intent may be considered.
For all others (metastatic disease), palliation is recommended.
239
Guidelines, surgery
alone is considered the standard of care and treatment of choice
for T1b and T2 cancers without nodal involvement or distant
metastasis.
Surgery in conjunction with a multimodal approach is
indicated for T1 to T4a tumors with lymph node metastases
Esophagectomy has the potential for high perioperative
morbidity (40% to 50%) and mortality (3% to 13%).
Lymph node status is an independent predictor of survival in
esophageal cancer
In patients undergoing esophagectomy without
neoadjuvant chemoradiation, the NCCN guidelines recommend
that 15 or more lymph nodes be removed for adequate staging
240
```
The role of endoscopic treatment of
esophageal cancer can be either for curative intent or palliation.
The former is reserved to mucosal tumors (T1a) confined to the
mucosa (M1 or intraepithelial), the lamina propria (M2), or the
muscularis mucosae (M3). These tumors have an extremely low
chance of harboring lymph node metastasis
```
In contrast to T1a tumors, T1b
tumors involving the submucosa have a higher risk of lymph node
metastasis, up to 56% in SM3 tumors
Ablation can be achieved with radiofrequency ablation (RFA)
or cryotherapy
241
The best predictors of esophageal cancer survival are depth of
invasion (T stage) and lymph node involvement (N stage).
Esophageal papillomas are asymptomatic, benign epithelial
tumors characterized endoscopically by a solitary, exophytic
lesion in the lower third of the esophagus (Fig. 48.18). They tend
to have a white or pink color. They have a soft consistency and
a smooth or slightly rough surface
242
Adenomas of the esophagus are rare and almost exclusively associated
with Barrett metaplasia
Leiomyosarcomas are the most common
| subtype and can be difficult to distinguish from benign leiomyomas.
243
GISTs are the most common mesenchymal tumor of the GI tract
The 2 most
common cancers to metastasize to the esophagus are melanoma
and breast cancer.
244
Leiomyomas are the most common benign esophageal tumors
EUS is the diagnostic test of choice; a leiomyoma is seen typically
arising from the muscularis propria. Only large (>5 cm), symptomatic
lesions require excision, which can be done endoscopically
for smaller tumors (using ESD techniques) or surgically
Fibrovascular polyps are benign esophageal lesions (Fig. 48.19).
They are almost exclusively seen in the cervical esophagus, likely
because of the relatively loose submucosal tissue and redundant
mucosa in this anatomic region
They are typically pedunculated
polyps consisting of blood vessels, adipose cells, and
stroma covered by normal squamous epithelium Some recommend EUS of larger polyps to
determine the presence of large blood vessels prior to excision.
245
Often, esophageal lipomas
exhibit the “pillow” sign—indentation or cushioning with
“palpation.” Superficial mucosal biopsies will usually be nondiagnostic.
Deeper samples from the submucosa will reveal welldifferentiated
adipocytes.
On EUS, a homogeneous, hyperechoic
| submucosal lesion with smooth outer margins is seen
246
A variceal pressure greater than
18 mm Hg during a bleeding episode is associated with failure
to control bleeding and predicts early rebleeding
In patients in whom no varices are detected on initial evaluation,
endoscopy to screen for varices should be repeated in 2
to 3 years. If small varices are detected on the initial examination,
endoscopy should be repeated in 1 to 2 years
247
Red color signs include
red “wale” markings, which are longitudinal
whip-like marks on the varix;
cherry-red spots, which
usually are 2 to 3 mm or less in diameter;
hematocystic spots,
which are blood-filled blisters 4 mm or greater in diameter;
and diffuse redness. The color of the varix can be white or
blue.
Esophageal varices may be small and straight
(grade I), tortuous and occupying less than one third of the
esophageal lumen (grade II), or large and occupying more
than one third of the esophageal lumen (grade III).
248
Small varices are 5 mm or less in diameter, whereas
| large varices are greater than 5 mm in diameter
```
Patients with large esophageal varices, Child-Pugh class C cirrhosis
(see later), and red color signs on varices have the highest
risk of variceal bleeding within one year
```
249
have demonstrated that a portal vein diameter greater
than 13 mm and the absence of respiratory variations in the
splenic and mesenteric veins are sensitive but nonspecific markers
of portal hypertension
A combination of liver and
spleen stiffness measured by acoustic radiation force impulse
elastography may also identify patients at risk for esophageal
varices
250
```
Causes of Portal Hypertension
COMMON
Cirrhosis
Schistosomiasis
Extrahepatic portal vein thrombosis
Idiopathic portal hypertension
Cardiac fibrosis
```
```
LESS COMMON
Nodular regenerative hyperplasia
Partial nodular transformation of the liver
Fibropolycystic liver disease
Sarcoidosis
Malignancy
Splanchnic arteriovenous fistula
HHT
```
251
DRUGS THAT DECREASE PORTAL BLOOD FLOW
Nonselective β-adrenergic blocking agents (e.g., propranolol, nadolol)
Somatostatin and its analogs
Vasopressin and terlipressin
DRUGS THAT DECREASE INTRAHEPATIC RESISTANCE
α1-Adrenergic blocking agents (e.g., prazosin)
Angiotensin receptor blocking agents
Nitrates
Following a single 250-μg bolus injection of somatostatin, portal
and azygos blood flow decrease, but the effect lasts only a
few minutes
Following IV administration, octreotide has a half-life in the
circulation of 80 to 120 minutes
252
Nonselective beta blockers such as propranolol
or nadolol are preferred. Blockade of β1-adrenergic
receptors in the heart decreases cardiac output. Blockade of
β2-adrenergic receptors, which cause vasodilatation in the mesenteric
circulation, allows unopposed action of α1-adrenergic
receptors and results in decreased portal flow. The combination
of decreased cardiac output and decreased portal flow
leads to a decrease in portal pressure. Nadolol has advantages
over propranolol in that it is excreted predominantly by the
kidney, has low lipid solubility, and is associated with a lower
risk of CNS side effects such as depression
An acute hemodynamic response (decrease in HVPG to
<12 mm Hg, or by 10%) 20 minutes after administration of IV
propranolol may predict the long-term reduction in bleeding
risk
253
Carvedilol is a drug that has both nonselective beta blocker and
weak α-receptor blockade activity. α-Receptor activity normally
increases resistance within the intrahepatic circulation.
Therefore, blockade of the α-receptor decreases intrahepatic
vascular resistance, which results in a further reduction in portal
pressure. Carvedilol may be associated with hypotension
and renal sodium retention and should be used cautiously in
patients with Child-Pugh class C cirrhosis.
Carvedilol is also
known to have antioxidant as well as antiproliferative actions
and may be superior to endoscopic variceal ligation in the
prevention of a first variceal bleed.62 In addition, carvedilol
may delay progression of small esophageal varices to large
esophageal varices in patients with cirrhosis
Carvedilol is started at a dose of
3.125 mg twice daily, and the dose is increased stepwise to a
maximum of 25 mg daily
254
Endoscopic variceal ligation is the preferred endoscopic
modality for control of acute esophageal variceal bleeding and
prevention of rebleeding; however, the utility of band ligation
in the treatment of gastric varices is limited.
```
DURING PROCEDURE
Aspiration pneumonia
Retrosternal chest pain
FOLLOWING PROCEDURE
Bleeding
Esophageal dysmotility
Esophageal stricture
Esophageal ulcers
Mediastinitis
Perforation
SYSTEMIC (USUALLY WITH SCLEROTHERAPY)
Mesenteric venous thrombosis
Pulmonary embolism
Sepsis
```
255
The Sengstaken-Blakemore tube is a triple-lumen tube: one
tube is for aspirating gastric contents, another allows inflation
of a gastric balloon to 200 to 400 mL in volume, and the third
inflates an esophageal balloon.
The Minnesota tube is a modified
Sengstaken-Blakemore tube, with the modifications being a larger
gastric balloon (500 mL) and provision of an additional lumen for
esophageal aspiration. The Linton-Nachlas tube has a single 600-
mL gastric balloon with lumens for aspirating both the stomach
and esophagus
256
Balloon tamponade can control bleeding for up
to 24 hours in approximately 80% to 90% of patients. The risk of
pulmonary aspiration is reduced by placement of an endotracheal
tube.
A TIPS reduces elevated portal pressure by creating a communication
between the hepatic vein and an intrahepatic branch of the
portal vein. A percutaneous transjugular approach is used to insert
the shunt.
257
TIPS functions as a side-to-side portacaval shunt and
has been used to treat complications of portal hypertension, mainly
variceal bleeding and refractory ascites, as well as Budd-Chiari
syndrome and hepatic hydrothorax
A platelet count greater than
60,000/mm3 and an INR less than 1.5 are recommended but are
not essential in an emergency
The most common indication for placement of TIPS is
refractory variceal bleeding.
258
The use of early TIPS (within 72
hours of control of variceal bleeding) in patients at high risk of
rebleeding (Child-Pugh class C, class B with active bleeding, or
a MELD score greater than 18 and a transfusion requirement of
greater than 4 units of red blood cells [RBCs]) is associated with
a reduced rate of treatment failure and mortality, without an
increased risk of hepatic encephalopathy, compared with continued
pharmacologic and endoscopic therapy.
TIPS may worsen liver function by depriving the liver of portal
venous blood, thereby increasing the risk of hepatic encephalopathy,
with decreased survival in some patients.
Factors associated with a poor prognosis include a
serum ALT level greater than 100 U/L, serum bilirubin level
greater than 3 mg/dL, and pre-TIPS hepatic encephalopathy
unrelated to bleeding
259
Child-Turcotte-Pugh Scoring System and Child-Pugh
Classification
Ascites None Slight Moderate/severe
Encephalopathy None Slight/moderate Moderate/severe
Bilirubin (mg/dL)
<2
2-3
>3
Albumin (g/dL)
>3.5
2.8-3.5
<2.8
Prothrombin time (seconds increased)
1-3
4-6
>6
Total Numerical Score Child-Pugh Class
5-6 A
7-9 B
10-15 C
260
Esophageal varices are present in approximately 40% of patients
with cirrhosis and in as many as 60% of patients with cirrhosis
and ascites
The best clinical predictor
of bleeding appears to be variceal size. The risk of bleeding
in patients with varices less than 5 mm in diameter is 7% by 2
years, and the risk in patients with varices greater than 5 mm in
diameter is 30% by 2 years
261
Even more important, however, is
the HVPG, because the risk of bleeding is virtually absent when
the HVPG is below 12 mm Hg
Approximately
half of patients with a variceal bleed stop bleeding spontaneously
because hypovolemia leads to splanchnic vasoconstriction,
which results in a decrease in portal pressure. Excessive
transfusions may, in fact, increase the chance of rebleeding
262
Active bleeding at endoscopy, a lower initial hematocrit value,
higher serum aminotransferase levels, higher Child-Pugh
class, bacterial infection, an HVPG above 20 mm Hg, and
portal vein thrombosis are associated with failure to control
bleeding at 5 days
Of patients who have stopped
bleeding, approximately one third will rebleed within the next
6 weeks.
263
Of all rebleeding episodes, approximately 40% will
take place within 5 days of the initial bleed.216 Predictors of
rebleeding include active bleeding at emergency endoscopy,
bleeding from gastric varices, hypoalbuminemia, renal insufficiency,
and an HVPG greater than 20 mm Hg.209 The risk of
death associated with acute variceal bleeding is 5% to 8% at 1
week and about 20% at 6 weeks
Alcohol as the cause of cirrhosis,
a higher serum bilirubin level, a lower serum albumin
level, hepatic encephalopathy, and HCC are additional factors
associated with an increased 6-week mortality rate.
264
All patients with large varices (diameter >5 mm) should be considered
for prophylactic therapy (primary prophylaxis) to prevent
variceal bleeding. The presence of additional endoscopic signs
such as red wales does not influence the decision regarding prophylactic
therapy.
A
resting systolic blood pressure less than 90 mm Hg indicates
that the patient is likely to be intolerant of beta blockers. In
other patients, the HVPG ideally should be measured at baseline
(Fig. 92.13). A long-acting preparation of propranolol or
nadolol may be started; the usual starting dose of long-acting
propranolol is 60 mg once daily and that of nadolol is 20 mg
once daily.
265
The dose of propranolol or nadolol can be increased gradually
every 3 to 5 days until the target heart rate of 25% below
baseline, or 55 to 60 beats/min, or the maximum tolerated dose
is reached,
Acute esophageal variceal bleeding
Two large-bore IV access lines should be inserted immediately.
RBCs should be transfused with the goal of maintaining the
hematocrit value around 25%. A restrictive strategy of transfusing
RBCs only when the Hgb level drops below 7 g/dL is associated
with improved survival in patients with Child-Pugh class A and B
cirrhosis, as compared with a strategy of transfusing when the Hgb
level drops below 9 g/dL
266
Excessive RBC transfusions may be
associated with risks of massive transfusion, including an increased
risk of hypocoagulability; on the other hand, excessive use of saline
is associated with ascites and the risk of abdominal compartment
control
In patients with active bleeding,
the airway needs to be protected, and endotracheal intubation
is advised. Antibiotics should be administered to all patients
to prevent bacteremia and spontaneous bacterial peritonitis
(see Chapter 93). Norfloxacin, 400 mg orally twice daily for 7
days, has been the preferred choice. When norfloxacin is not
available (as in the USA), ciprofloxacin 500 mg orally twice
daily for 7 days may be administered
267
IV ceftriaxone, 1 g every 24 hours for 7 days;
ciprofloxacin, 400 mg every 12 hours; or levofloxacin, 500 mg
every 24 hours is recommended
Terlipressin is the first choice in many other countries
because it has been associated with improved survival.235 Pharmacologic
treatment should be continued for up to 5 days to prevent
early rebleeding; however, a 24-hour course and a 72-hour course
of terlipressin may be equally effective when used in conjunction
with variceal ligation
268
Bleeding cannot be controlled in approximately 10% to 15% of
| patients, as defined by any of the following 3 criteria:
(1) transfusion
of 4 units of RBCs or more to maintain the hematocrit value
above 25%, (2) inability to increase the systolic blood pressure by
20 mm Hg or to greater than 70 mm Hg, or (3) persistence of
a heart rate greater than 100 beats/min
269
Rebleeding is defined
as recurrence of bleeding after initial control for 24 hours during
which the vital signs and Hgb level are stable.
carried out
When 2 sessions of
endoscopic treatment within a 24-hour period have failed to control
variceal bleeding, salvage therapies such as TIPS should be
270
In practice, the first
endoscopic session is carried out 7 to 14 days after the initial variceal
ligation to control bleeding.
One-week ligation intervals may
lead to more rapid eradication of varices than 2-week intervals but
without a reduced risk of bleeding.
