Gastric Flashcards
(106 cards)
1
Q
Gastric volvulus results when the stomach twists on itself, but
rarely occurs unless there is an associated
A
diaphragmatic hernia.
2
Q
, the stomach folds on its
short axis, which runs across the stomach from the lesser curvature
to the greater curvature, with
the antrum twisting anteriorly and superiorly.
A
In mesenteroaxial volvulus
Mesenteroaxial volvulus
is often incomplete and intermittent, manifesting chronic symptoms.
3
Q
organoaxial volvulus, the stomach twists along its long
axis, which passes through the esophagastric junction region to
the pylorus.
A
In most cases, the antrum rotates anteriorly and
superiorly and the fundus posteriorly and inferiorly, twisting the
greater curvature at some point along its length
4
Q
Acute gastric volvulus causes sudden severe pain in the upper
abdomen or lower chest, associated with the inability to swallow.
A
Persistent unproductive retching is common.
5
Q
The combination of pain, unproductive
retching, and inability to pass a nasogastric tube is called
A
Borchardt triad
If the volvulus is associated with a diaphragmatic
hernia, plain chest or abdominal films will show a large gas-filled
structure in the chest
6
Q
Acute gastric volvulus is an emergency, with a mortality rate in
A
the vicinity of 30%.
7
Q
signs of gastric infarction are not present,
acute endoscopic detorsion may be considered. Using fluoroscopy,
the endoscope is advanced to form an alpha loop in the
proximal stomach
A
The tip is passed through the area of torsion
into the antrum or duodenum if possible, avoiding excess
pressure. Torque may then reduce the gastric volvulus.
8
Q
type 1 gastroesophageal
varices (GOV1) extend 2 to 5 cm below the gastroesophageal
junction and are in continuity with esophageal varices;
A
type 2 gastroesophageal varices (GOV2) are in the cardia and
fundus of the stomach and in continuity with esophageal varices
9
Q
varices that occur in the fundus of the stomach in the absence of
esophageal varices are called isolated gastric varices type 1 (IGV1),
A
whereas varices that occur in the gastric body, antrum, or pylorus
are called isolated gastric varices type 2 (IGV2).
10
Q
Approximately 25% of patients with portal hypertension have
gastric varices, most commonly GOV1, which comprise approximately
70% of all gastric varices. Intrahepatic causes of portal
hypertension may be associated with both GOV1 and GOV2.
Splenic vein thrombosis usually results in IGV1, but the most common
cause of fundal gastric varices may be cirrhosis
A
Gastric varices typically occur in association with advanced portal
hypertension. Bleeding is thought to be more common in patients
with GOV2 and IGV1 than in those with other types of gastric
varices; in other words, bleeding is more common from fundal varices
than from varices at the gastroesophageal junction
11
Q
Gastric varices, however,
tend to be larger in diameter than esophageal varices.
A
Gastric
varices are supported by gastric mucosa, whereas esophageal varices
tend to be unsupported in the lower third of the esophagus
12
Q
Although gastric varices
have been thought to bleed less frequently than esophageal varices,
the bleeding rates probably are comparable if patients are matched
for the severity of cirrhosis (Child-Turcotte-Pugh score
A
Large gastric varices (>20 mm diameter), especially in patients
with a MELD score above 17, are most likely to bleed.
13
Q
Cyanoacrylate glue injection
may be more effective than beta blocker therapy in preventing
gastric variceal bleeding246 but is not currently recommended
until confirmed by larger studies. TIPS is also not recommended
for the primary prevention of gastric variceal bleeding. BRTO has
been used in uncontrolled studies to prevent bleeding from gastric
varices, with some success.
A
acute gastric variceal hemorrhage and includes volume
resuscitation, avoidance of overtransfusion, and antibiotic prophylaxis
with norfloxacin, 400 mg twice daily, or ciprofloxacin,
500 mg twice daily, for 7 days. EGD is carried out after patients
have been volume resuscitated and stabilized and often following
endotracheal intubation to protect the airway.
14
Q
blood is found in the
stomach and gastric varices with a “white nipple sign” (indicating
a fibrin-platelet plug) are seen in the absence of other causes
of bleeding; or gastric varices are noted in the absence of other
lesions in the esophagus and stomach.
A
Medical
management with vasoactive agents should be started as early as
possible, preferably at least 30 minutes before endoscopic therapy
is carried out. The preferred endoscopic therapy for fundal gastric
variceal bleeding is injection of polymers of cyanoacrylate, usually
N-butyl-2-cyanoacrylate
15
Q
Obliteration of the varices occurs
when the injected cyanoacrylate adhesive hardens on contact with
blood.
A
The endoscope may be damaged by the glue, but the risk is
minimized if silicone gel is used to cover the tip of the instrument
and suction is avoided for 15 to 20 seconds following injection
16
Q
Cyanoacrylate injection has been
found to be superior to both variceal band ligation and sclerotherapy
using alcohol.251 Complications of cyanoacrylate injection
include bacteremia and variceal ulceration
A
For injection of GOV2 or IGV1, a retroflexed endoscopic
approach is recommended.
17
Q
It is much easier to
obliterate GOV1 than GOV2 or IGV1. IGV1 are the most difficult
gastric varices to obliterate and, when present, should prompt
early consideration of definitive treatment such as portosystemic
shunting if cyanoacrylate is not available.
A
Band ligation of varices greater than
10 mm in diameter is usually unsafe. Ligation is safest if the varices
are in the cardia of the stomach
18
Q
If endoscopic and pharmacologic therapies fail to control gastric
variceal bleeding, then a Linton-Nachlas tube may be passed
as a temporizing measure. Most patients in whom endoscopic and
pharmacologic treatment fails to control gastric variceal bleeding
will require a TIPS, which can control bleeding in greater than
90% of patients—
A
Patients require an average of 2 or 3 sessions for obturation of
gastric varices with cyanoacrylate polymers
19
Q
Comparison of Portal Hypertensive Gastropathy (PHG) and
GAVE
Feature
PHG
Proximal stomach
Mosaic pattern Present
Red color signs Present
A
GAVE
Distal stomach
Mosaic pattern Absent
Red color signs Present
20
Q
The stomach volume
ranges from approximately 30 mL in a neonate to 1.5 to 2 L in
adulthood.
The stomach is recognizable in the fourth week of gestation
as a dilation of the distal foregut
A
As the stomach
enlarges, the dorsal aspect grows more rapidly than the ventral
aspect, therefore forming the greater curvature. Additionally,
during the enlargement process the stomach rotates 90 degrees orienting the greater curvature (the
dorsal aspect) to the left and the lesser curvature (ventral aspect)
to the right.
21
Q
right vagus nerve innervating
the posterior stomach wall (the primordial right side) and
the left vagus nerve innervating the anterior wall (the primordial
left side).
A
The esophagogastric
junction generally lies to the left of the T10 vertebral body,
1 to 2 cm below the diaphragmatic hiatus. The gastroduodenal
junction lies at L1 and generally to the right of the midline in
the recumbent fasted individual
22
Q
The esophagogastric
junction generally lies to the left of the T10 vertebral body,
1 to 2 cm below the diaphragmatic hiatus. The gastroduodenal
junction lies at L1 and generally to the right of the midline in
the recumbent fasted individual
A
The greater curvature forms the left lower stomach border,
whereas the lesser curvature forms the right upper border. Posteriorly,
portions of the pancreas, transverse colon, diaphragm,
spleen, and apex of the left kidney and adrenal gland bound the
stomach.
23
Q
The posterior wall of the stomach actually comprises
the anterior wall of the omental bursa, or lesser peritoneal sac.
Anteriorly, the liver bounds the stomach, whereas the inner
aspect of the anterior abdominal wall bounds the anterior left
lower aspect.
A
The stomach is completely invested by peritoneum,
except for a small bare area at the esophagogastric junction.
This peritoneum passes as a double layer from the lesser curvature
to the liver as the gastrohepatic portion of the lesser
omentum and then hangs down from the fundus and greater
curvature as the greater omentum, extending to the transverse
colon (as the gastrocolic ligament), spleen (as the gastrosplenic
ligament), and diaphragm (as the gastrophrenic
ligament).
24
Q
The arterial blood supply to the stomach is derived from branches
of the celiac artery—common hepatic, left gastric, and splenic
arteries
A
that form 2 arterial arcades situated along the lesser
curvature and the lower two thirds of the greater curvature
25
The
lesser curvature is supplied from above by the left gastric artery
and from below by the right gastric artery, a branch of the common
hepatic artery or gastroduodenal artery (which is a branch
of the common hepatic artery).
The greater curvature below the
fundus is supplied from above by the left gastroepiploic artery (a
branch of the splenic artery) and from below by the right gastroepiploic
artery (a branch of the gastroduodenal artery). The right
and left gastroepiploic arteries usually terminate by anastomosing,
therefore completing the greater curvature arterial arcade;
occasionally they end without anastomosis
The greater curvature below the
fundus is supplied from above by the left gastroepiploic artery (a
branch of the splenic artery) and from below by the right gastroepiploic
artery (a branch of the gastroduodenal artery
26
The arterial supply to
the gastric fundus and left upper aspect of the greater curvature is
via the short gastric arteries, which arise from the splenic artery
the short gastric arteries, which arise from the splenic artery.
The venous drainage of the stomach generally accompanies
the arterial supply, emptying into the portal vein or 1 of its tributaries,
the splenic or superior mesenteric veins
27
The left gastroepiploic vein becomes the
splenic vein and later receives the short gastric veins, therefore
draining the fundus and upper great curvature of the stomach.
The inferior gastric region drains into subpyloric
and omental nodes, then the hepatic nodes, terminating in the
celiac nodes
The superior gastric or lesser curvature region
lymph drains into the left and right gastric nodes adjacent to their
respective vessels and terminates in the celiac nodes.
28
The gastric sympathetic innervation is derived from preganglionic
fibers arising predominantly from T6 to T8 spinal nerves,
The parasympathetic innervation is via the right and left vagus
nerves, which form the distal esophageal plexus, and gives rise to
the posterior and anterior vagal trunks near the gastric cardia.
29
The luminal surface of the gastric wall forms thick, longitudinally
oriented folds, or rugae, that flatten with distention. Four layers
make up the gastric wall: mucosa, submucosa, muscularis propria,
and serosa
The mucosa of the cardia, antrum,
| and pylorus is somewhat paler than that of the fundus and body.
30
It is within the fundic and body mucosa that most of the functional
secretory elements of the stomach are located
submucosa, immediately deep to the mucosa, provides
the dense connective tissue skeleton of collagen and elastin fibers.
Lymphocytes, plasma cells, arterioles, venules, lymphatics, and
the submucosal plexus are also contained within the submucosa
The third tissue layer, the muscularis propria, is a combination of
3 muscle layers: inner oblique, middle circular, and outer longitudinal.
The inner oblique muscle fibers course over the gastric
fundus, covering the anterior and posterior aspects of the stomach
wall; the middle circular fibers encircle the body of the stomach,
thickening distally to become the pyloric sphincter; and the outer
longitudinal muscle fibers course primarily along the greater and
lesser curvatures of the stomach
31
inner oblique, middle circular, and outer longitudinal.
The inner oblique muscle fibers course over the gastric
fundus, covering the anterior and posterior aspects of the stomach
wall; the middle circular fibers encircle the body of the stomach,
thickening distally to become the pyloric sphincter; and the outer
longitudinal muscle fibers course primarily along the greater and
lesser curvatures of the stomach
32
typical gland is subdivided into 3
areas: the isthmus (where surface mucous cells predominate), the
neck (where parietal and mucous neck cells predominate), and the
base (where chief cells predominate, along with some parietal and
mucous neck cells).
Chief cells, also known as zymogen cells, predominate in deeper
layers of the oxyntic glands. These pyramid-shaped cells play
a role in synthesis and secretion of pepsinogens I and II.
33
Those cells containing
granules that reduce silver without pretreatment are called argentaffin
cells. Argentaffin cells that stain with potassium dichromate
are enterochromaffin (EC) cells; most ECs contain serotonin
weeks 5
and 6 of embryologic development, the duodenal lumen is temporarily
obliterated owing to proliferation of its mucosal lining
34
patients with gastric
erosion(s) or ulcer(s), thick gastric fold(s), gastric polyp(s) or
mass(es), and for diagnosis of Hp infection (discussed later). Two
biopsies should be taken from the antrum (lesser and greater curvatures),
one from the incisura angularis, and 2 more from the
gastric body (lesser and greater curvatures)
Acute gastritis, characterized by dense infiltration of the stomach
with neutrophilic leukocytes
35
Phlegmonous (suppurative) gastritis is an infection of the gastric
submucosa and muscularis propria, often sparing the mucosa
The mortality rate of phlegmonous gastritis is close to 70%, Vancomycin and piperacillin/tazobactam is one empiric
regimen that can be used
36
Chronic gastritis is much more common than acute gastritis,
| although it may be clinically silent
are risk factors for other diseases such as PUD and gastric neoplasms,
including adenocarcinoma and lymphoma (MALToma),
37
Three types of chronic gastritis are recognized: diffuse antral
gastritis which is usually due to Hp infection, environmental
metaplastic atrophic gastritis (EMAG), and autoimmune metaplastic
atrophic gastritis
Hp is a gram-negative helical- or spiral-shaped flagellated bacterium.
38
A form of Hp gastritis characterized by mucosal infiltration
by plasma cells that contain Russell bodies (Russell body gastritis)
has been described
A form of Hp gastritis that can be
recognized endoscopically is nodular gastritis, which can resolve
following eradication of the organism from the
Nodular gastritis/gastropathy is recognized by its chicken-skin
appearance and can be seen in other conditions, including Crohn
disease, syphilitic gastritis, lymphocytic (varioliform) gastritis,
collagenous gastritis (all discussed later), and in AA-amyloidosis
39
Hp infection is the most common chronic bacterial infection in
humans. Estimates suggest that over 50% of the world’s population
is infected with the bacterium, including 70% to 80% of
populations in developing nations.
key risk factor for infection is socioeconomic status during
childhood. Infection is commonly acquired at an early age, particularly in developing countries where the majority of children
become infected before the age of 10.
40
serologic
evidence of Hp infection is uncommon in children before
age 10, but rises to 10% in adults between 18 and 30 years of
age, and further increases to 50% in those age 60 or older
Organism loads are 100-fold higher in vomitus
when compared with stool and saliva; organisms are also present
in aerosolized vomitus out to 1.2 m during the act of vomiting.
41
Hp contain 6 to 8 flagella at one end of their bodies and flagella-
mediated motility is one of the few characteristics shown
to be required for successful Hp colonization of the host
Exposure of Hp to low gastric pH levels increases expression
of bacterial genes encoding urease.55 Urease helps Hp adapt to
the acidic gastric milieu, allowing a more neutral pH to occur
near the bacteria as its urease splits urea into CO2 and ammonia
(NH3), with the NH3 reacting with H+ to produce ammonium
ion (NH4
+)
42
Hp show strict tropism for gastric-type mucosa, including in
| nongastric regions of the GI tract where there is gastric metaplasia
Metaplasia may also be associated with hypochlorhydria/
achlorhydria, encouraging overgrowth of the stomach with other
(non-Hp) species of bacteri
43
A key interaction between Hp and gastric epithelium is mediated
by a segment of bacterial DNA referred to as the cag pathogenicity
island (cag PAI).
identify Hp in a gastric biopsy specimen: biopsy urease testing,
histology, and culture. The choice of method depends on the
clinical situation, cost, availability, and test accuracy.125 For each
method, either 1 or 2 biopsies are obtained from both the antrum
and corpus
44
```
Serology (qualitative or quantitative IgG)
Widely available
Inexpensive
Good NPV
Poor PPV if Hp prevalence is low
Not useful after treatment
```
Urea breath (13C or 14C)
Identifies active infection
Accuracy (PPV, NPV) not affected by Hp prevalence
Useful both before and after treatment
Availability and reimbursement inconsistent
Accuracy affected by PPI and antibiotic use
Small radiation dose with14C test
Stool antigen
Identifies active infection
Accuracy (PPV, NPV) not affected by Hp prevalence
Useful both before and after treatment
Fewer data available
Accuracy affected by PPI and antibiotic use
To improve sensitivity in such patients, stopping the potentially
problematic medication and delaying EGD for 2 weeks (if possible)
can be considered, and testing multiple (>2) biopsy samples
from the antrum and corpus may be attempted.
45
Histologic
examination had been considered the gold standard for identifying
infection, with reported sensitivity and specificity as high as
95% and 98%, respectively.
Culture of mucosal biopsies is difficult because Hp is fastidious
and slow growing, requiring specialized media and growth
environment
46
In chronic atrophic gastritis (gastric atrophy),148-168 loss of
specialized cells within gastric glands, such as parietal and chief
cells, leads to a reduction or absence of their secreted products,
such as intrinsic factor (IF) and hydrochloric acid (hypochlorhydria
or achlorhydria) as well as pepsinogen, with an increased risk
of adverse consequences such as vitamin B12 malabsorption, gastric
bacterial overgrowth, and enteric infections
Two types of chronic atrophic gastritis are recognized (Fig.
52.2, and Fig. 52.3B and C): an environmental metaplastic EMAG, also called multifocal
atrophic gastritis, and an autoimmune metaplastic AMAG, also called diffuse corporal atrophic
gastritis.
EMAG (usually due to chronic Hp infection) and
AMAG (usually due to autoreactive T and B/plasma cells against
various antigens of the parietal cell)
47
EMAG is characterized by involvement of both the gastric
| antrum and corpus with glandular atrophy and IM
important for endoscopists to obtain at least 2 biopsies from the
antrum, 1 from the incisura angularis, and 2 from the gastric body
in order for the pathologist to be able to render a diagnosis of
EMAG
48
AMAG, also called diffuse corporal atrophic gastritis, is an autoimmune
destruction of glands in the corpus of the stomach. AMAG
is the pathologic process underlying pernicious anemia, an autoimmune
disorder
Examination of mucosal biopsy specimens shows inflammatory
debris, chronic active gastritis, and enlarged cells with CMV
inclusion bodies indicative of an active infection (Fig. 52.7A).
“Owl-eye” intranuclear inclusions are the hallmark of CMV infection
in routine H&E histologic preparations and may be found in
vascular endothelial cells, mucosal epithelial cells, and connective
tissue stromal cells IV ganciclovir or foscarnet, along with reducing immunosuppression,
if feasible
49
Barium-air double-contrast radiographs show a cobblestone pattern,
shallow ulcerations with a ragged contour, and an interlacing
network of crevices filled with barium that corresponds to
areas of ulceration.
Measles, caused by rubeola virus, has many GI manifestation,
including, rarely, gastritis. The characteristic histologic pattern is
of numerous multinucleated giant cells (Warthin-Finkeldey cells
50
Erosions and acute ulcers of the gastric mucosa may occur rapidly
after major physical or thermal trauma, shock, sepsis, or head
injury. These are often referred to as stress ulcers
Injury to the stomach from external ionizing radiation can be
classified as acute (<6 months) or chronic (>1 year) (see Chapter
41).302,303 It is thought that the tolerance level for radiationinduced
gastropathy is approximately 4500 cGy. With a gastric
dose of ≥5500 cGy, most patients will develop clinical evidence
of gastropathy and/or gastric ulcer formation
51
Ménétrier’s disease is typically but not always associated with
protein-losing gastropathy (see Chapter 31) and with hypochlorhydria,
whereas its rare hyperplastic, hypersecretory variant is
associated with increased or normal acid secretion and parietal
and chief cell hyperplasia, with or without excessive gastric protein
loss. Ménétrier’s disease has been associated with infection
with Hp, CMV, and HIV.
Historically, recommended Hp
treatment regimens generally included a PPI plus 2 antibiotics
for 10 to 14 days.
However, recent recommendations have
moved toward a standard 14-day treatment duration, as shorter
treatment durations are associated with reduced effectiveness
52
quadruple combinations of a PPI and 3 antibiotics
| or antimicrobial agents are now generally recommended
Clarithromycin triple therapy comprises the twice-daily combination
of clarithromycin 500 mg, amoxicillin 1000 mg, and a
PPI in standard dose taken for 14 days
53
Bismuth-based quadruple therapy is another recommended
primary treatment option. It consists of the combination of a
bismuth salt (e.g., bismuth subsalicylate or bismuth subcitrate),
tetracycline, metronidazole and a PPI for 10 to 14 days. Because
this regimen contains neither clarithromycin nor amoxicillin,
it is an appropriate choice for patients who have previously
used macrolides, who reside in areas with high (≥15%) macrolide
resistance, and for those who are truly penicillin-allergic
```
Concomitant therapy (also known as nonbismuth-based quadruple
therapy) is the quadruple combination of clarithromycin
```
54
```
Clarithromycin triple
therapy
PPI, clarithromycin 500 mg, and
amoxicillin 1000 mg, each twice
daily (or, if penicillin allergic,
metronidazole 500 mg 3 times daily
in place of amoxicillin)
```
14
```
Bismuth-based
quadruple therapy
PPI twice daily, bismuth subcitrate
or subsalicylate 4 times daily,
tetracycline 500 mg 4 times daily,
and metronidazole 250 to 500 mg 3
or 4 times daily
```
10-14
55
```
Concomitant therapy PPI, clarithromycin 500 mg, and
amoxicillin 1000 mg, and a
nitroimidazole 500 mg, each twice
daily
10-14
```
Sequential therapy PPI and amoxicillin 1000 mg, both
twice daily
5-7
PPI, clarithromycin 500 mg, and a
nitroimidazole 500 mg, each twice
daily
5-7
56
Hybrid therapy PPI and amoxicillin 1000 mg, both
| twice daily
PPI, clarithromycin 500 mg, amoxicillin
1000 mg, and a nitroimidazole 500
mg, each twice daily
57
Bismuth-based quadruple
therapy
(see Table 52.7)
14 Strong Low Appropriate for patients who failed in
```
Levofloxacin
triple therapy
(see Table 52.7)
14 Strong Moderate
(For duration, low)
Appropriate for patients who failed initial treatment with a
clarithromycin-based regimen
```
58
Sequential therapy involves a 2-step regimen, each of 5 to 7
days in duration. In the first step, a PPI is given with amoxicillin
alone. In the second step, the PPI is given with clarithromycin
and a nitroimidazole (typically tinidazole but possibly also
metronidazole). This approach was developed in Europe where
it had been widely adopted. It has not been extensively evaluated
in trials conducted within North America but has not been
found to be superior to other regimens
A
combination of levofloxacin, omeprazole, nitazoxanide (“Alinia”)
and doxycycline (referred to as “LOAD”) was found to be superior
to clarithromycin-based triple therapy in a US randomized
controlled trial.364 No further trials have been reported with this
regimen.
59
The most important predictors of failure of treatment are antibiotic
resistance and poor adherence to treatment
An ulcer in the GI tract can be defined as a 5 mm or larger break in
the lining of the mucosa, with appreciable depth at endoscopy or
with histologic evidence of submucosal extension. An erosion is a
break less than 5 mm
60
The most frequent complication from PUD is bleeding
The principal risk factors of PUD are Hp infection and NSAID
| use
61
Most patients with Hp infection have a pan-gastritis involving
both the antral and fundic mucosa that lowers gastric acid secretion13
and predisposes to GU formation
Regular use of
| NSAIDs increases the odds of GI bleeding up to 5- to 6-fold
62
This low risk of ulcer rebleeding
after eradication of Hp was not seen in patients with bleeding
ulcers who continued to take NSAIDs
Smoking, stress, type A personality, and excessive alcohol
| use are some of the risk factors implicated for PUD.
63
Importantly, patients with
a history of idiopathic bleeding ulcers have a 4-fold increased risk
of recurrent ulcer bleeding and more than 2-fold increase in mortality
compared to patients with history of Hp ulcers
The predominant symptom of patients with uncomplicated PUD
is epigastric pain. Pain is typically associated with hunger, occurs
at night, and is often relieved by food and antacids
64
EGD is the procedure of choice for diagnosis of uncomplicated
PUD
If a DU or GU is found during EGD, gastric mucosal
biopsies should be obtained for a rapid urease test to diagnose
Hp infection
Biopsies should also be taken
from the edges of GUs because of risk of gastric cancer.
65
if the GU biopsies are benign, EGD is repeated 8
weeks later to confirm healing of the GU, because up to 4% of
apparently benign GUs at initial endoscopy are subsequently
found to be malignant.
Alarm Features in Patients With UGI Symptoms*
Age older than 55 years with new-onset dyspepsia
Family history of UGI cancer
GI bleeding, acute or chronic, including unexplained iron deficiency
Jaundice
Left supraclavicular lymphadenopathy (Virchow node)
Palpable abdominal mass
Persistent vomiting
Progressive dysphagia
Unintended weight loss
*These features should prompt EGD and often other testing to establish a
definitive diagnosis (
66
uninvestigated dyspepsia who are below 60 years of age should
have a noninvasive test H and treatment if positive. Those with
a negative test or do not respond to this approach should receive
a trial of PPI therapy. Tricyclic antidepressants or prokinetic
therapies can be tried if they are not responsive to PPI therapy
Patients older than age 60 presenting
with new-onset upper abdominal symptoms suggestive of PUD
should therefore be referred for EGD
67
Most physicians do not use antacids as primary therapy to
heal ulcers but instead recommend their use to relieve dyspeptic
symptoms. The most common adverse effect of magnesium-containing
antacids is diarrhea. In contrast, aluminum- and calciumcontaining
antacids may cause constipation.
When administered in the evening,
H2RAs are effective in suppressing nocturnal acid output.46
H2RAs are well absorbed after oral dosing, and their absorption
is not affected by food.
H2RA nizatidine does not undergo first-pass
metabolism, and its bioavailability approaches 100% with oral
dosing.
68
PPIs decrease gastric acid secretion through inhibition of H+,
K+-ATPase, the proton pump of the parietal cell
Absorption of the enteric-coated PPIs may be erratic,
and peak serum concentrations are not achieved until 2 to 5 hours
after oral administration. Although the plasma half-life of PPIs is
short (≈2 hours), the duration of acid inhibition is long as a result
of covalent binding of the active metabolite of the prodrug to the
H+, K+-ATPase
69
```
TABLE 53.1 Risk Factors for NSAID Ulcers*
Risk factor Risk ratio
History of complicated ulcer 13.5
Use of multiple NSAIDs (including aspirin, COX-2 inhibitors) 9
Use of high doses of NSAIDs 7
Use of an anticoagulant 6.4
History of an uncomplicated ulcer 6.1
Age >70 years 5.6
Hp infection 3.5
Use of a glucocorticoid 2.2
*Not all NSAIDs pose the same risk.
```
Current evidence indicates that COX-2 inhibitors are as effective
as a combination of nonselective NSAIDs combined with a
PPI in patients at risk for ulcers.
70
Low CV risk
Low GI
NSAID at the lowest effective dose
Mod GI
NSAID plus a PPI, or celecoxib alone
Hi GI
Celecoxib plus a PPI
High CV risk†
Low GI
Naproxen or celecoxib, plus a PPI
mod
Naproxen or celecoxib, plus a PPI
Hi
Celecoxib plus a PPI if simple analgesics
*Low GI risk denotes no risk factors (see Table 53.1); moderate GI risk denotes 1 or 2 risk factors; high GI risk denotes ≥3 risk factors, prior complicated
ulcer, or concomitant use of low-dose aspirin or anticoagulants. All patients with a history of ulcer who require NSAIDs should be tested for Hp, and if
infection is present, eradication therapy should be given (see Chapter 52).
†High CV risk denotes the requirement for prophylactic low-dose aspirin for primary or secondary prevention of serious CV events.
CV, cardiovascular.
71
Low ulcer risk: no risk factors. Patients without risk factors
(see Table 53.1) are at very low risk of ulcer complications
with NSAID use (≈1% per year). Rational use of NSAIDs,
including avoidance of high doses of NSAIDs and use of a less
ulcerogenic NSAID (e.g., ibuprofen, diclofenac) at the lowest
effective dose is a cost-effective approach
Moderate ulcer risk: 1 or 2 risk factors. These patients should
receive combination therapy with an antiulcer agent (a PPI or
misoprostol) and an NSAID. Alternatively, substitution with
celecoxib alone is as effective as the combination therapy mentioned
earlier.
72
High ulcer risk: 3 or more risk factors, history of ulcer complications,
or concomitant use of low-dose aspirin, glucocorticoids,
or anticoagulant therapy
In general, NSAIDs should be avoided
in these patients, not only because of the high risk of ulcer complications
but also owing to the serious consequences of ulcer
complications in the presence of comorbidities. Glucocorticoid
therapy (without NSAID) can be considered if short-term antiinflammatory
therapy is required for acute, self-limiting arthritis
If regular anti-inflammatory therapy is required for
chronic arthritis, the combination of celecoxib and a PPI offers
the best GI protection
73
Defining patients with high cardiovascular risk remains arbitrary.
The American Heart Association recommends that aspirin
should be considered in all apparently healthy men and women
whose 10-year risk for a cardiovascular event is 10% or above.
Ibuprofen can attenuate the cardioprotective
effect of aspirin, possibly through competitive binding
to platelet COX-1, and concomitant use of ibuprofen and
low-dose aspirin, therefore, should be avoided
74
If an NSAID is
deemed necessary in patients at high cardiovascular risk, current
evidence suggests that either celecoxib at moderate dose (200 mg/
day) or naproxen can be considered
One major drawback of concomitant
use of NSAIDs such as naproxen and low-dose aspirin
is that the combination will markedly increase the risk of ulcer
complications; thus, combination of celecoxib and low-dose aspirin
may be the best available option for patients with high GI and
high cardiovascular risk who require NSAIDs for long term
75
Volume resuscitation should
take priority and precede endoscopy. Features of liver disease
should call attention to the possibility of bleeding from esophagogastric
varices rather than an ulcer.
Early endoscopy is generally defined as EGD performed within
24 hours of the patient’s admission. In patients with signs of
active UGI bleeding, urgent endoscopy establishes a diagnosis
and offers a possible intervention. RCTs demonstrated that early
endoscopy in patients at low risk for rebleeding allowed early
hospital discharge, reduced resource utilization, and facilitated
management as outpatients.
76
The Rockall
scoring system is a composite score using pre- and postendoscopy
clinical parameters to predict mortality.
The Glasgow Blatchford score (GBS), on the other hand, uses
only clinical parameters to predict the need for intervention and
is calculated from patient’s Hgb level and blood urea concentration,
pulse and systolic blood pressure on admission, the presence
or absence of melena or syncope, as well as evidence of cardiac or
hepatic failure.
77
GBS score of 1 appears to be the
threshold for outpatient management. The GBS score, however,
does not define a cutoff value above which urgent endoscopy
becomes mandatory.
Type I: Active bleeding:
Ia: Spurting hemorrhage (Fig. 53.4)
Ib: Oozing hemorrhage (see Fig. 53.4)
Type II: Stigmata of recent hemorrhage:
IIa: Nonbleeding visible vessel (see Fig. 53.4)
IIb: Adherent clot (see Fig. 53.4)
IIc: Flat pigmentation (see Fig. 53.4)
• Type III: Clean-base ulcers
78
Actively bleeding ulcers and ulcers with nonbleeding visible
vessels (“protuberant discoloration” or a “sentinel clot”) warrant
endoscopic therapy
concluded that clot removal followed by endoscopic treatment of
the vessel underneath lowers the risk of recurrent bleeding from
30% to 5%.
79
sentinel clot, is often used synonymously with visible
vessel.117 It represents a fibrin clot, which plugs the rent in an
eroded artery. As the ulcer begins to heal, the clot resolves leaving
a flat pigmentation to the ulcer base, which eventually disappears
from the ulcer floor. This evolution of a bleeding vessel
usually takes less than 72 hours. Ulcers with a flat pigmentation
or a clean base do not warrant endoscopic therapy
The 30 day re-bleeding rate was lower with the use
| of a Doppler probe to guide the treatment endpoint
80
The rationale for antisecretory therapy in bleeding PUD is based
on the fact that both pepsin activity and platelet aggregation are
pH dependent. An ulcer stops bleeding when a fibrin or platelet
plug blocks the rent in a bleeding artery. When gastric pH
exceeds 4, pepsin is inactivated, preventing enzymatic digestion of
blood clots.
A gastric pH of 6 or greater is critical for clot stability
and hemostasis.
GU or DU who were receiving either a high dose
of omeprazole (IV bolus 80 mg, followed by 8 mg/hr) or a high
dose of ranitidine (IV bolus 50 mg, followed by 0.25 mg/kg/hr).
The gastric pH exceeded 6 with omeprazole 99.9% of the time,
but less than 50% of the time in patients receiving ranitidine
81
Perforation of a GU or DU (Fig. 53.5) is a surgical emergency
that may be the initial manifestation of PUD, especially in
patients using NSAIDs. Ulcer perforation is associated with a
mortality approaching 30%. Older adults with significant comorbid
illnesses and a delay in performing surgery have the worst
prognosis.
Perforated gastroduodenal ulcer carries a high mortality rate
one third of them caused by persistent leaks
Large perforations
(>10 mm) suggest sizable ulcerations and should also be
managed by laparotomy; often, gastric resections are required in
such patients.
82
GU accounts for approximately 20% of perforated peptic
ulcers
Malignancy is seen in approximately 6% of perforated
GUs
Gastric outlet obstruction is now an infrequent complication of
PUD. Its clinical manifestations—nausea and postprandial vomiting,
abdominal fullness, pain, and early satiety
83
Patients with obstructing peptic ulcers are often volume depleted.
The loss of fluid, hydrogen ions, and chloride ions in the vomitus
leads to hypochloremic, hypokalemic metabolic alkalosis.
Endoscopic balloon dilation has been used successfully in patients
with gastric outlet obstruction from PUD
84
The use of a balloon
is preferred because its inflation produces a uniform radial force,
which has a theoretical advantage over the longitudinal shearing
force associated with the use of conventional dilators
many authorities recommend dilation
to 15 mm, which is often associated with relief of symptoms
Respiratory failure (OR 15.6) and coagulopathy (OR 4.3) were
independent predictive factors for bleeding stress ulcers. In
2015, a prospective study152 of 1034 patients admitted to ICUs
was published; clinically important GI bleeding occurred in
2.6% of patients. Those with 3 or more comorbid illnesses,
liver disease, receiving renal replacement therapy, and with
a high organ failure score were at risk. Patients in the ICU
with traumatic brain injuries and burns also belong to a highrisk
group of developing GI bleeding.
85
PPIs were more effective
for preventing clinically important bleeding than H2RA (OR
0.38), sucralfate (OR 0.30), or placebo (OR 0.24). PPIs, however,
increased the risk of nosocomial pneumonia compared with
H2RA (OR 1.27), sucralfate (OR 1.65), and placebo
40 mg of intravenous PPI or placebo and found that deaths by 90
days were similar between groups (31.1% vs. 30.4%). The rate
of composite adverse events (gastrointestinal bleeding, Clostridium
difficile infection, pneumonia, or myocardial ischemia) were
comparable (21.9 vs. 22.6%). There were fewer clinically important
bleeding events in the PPI group
86
Gastric cancer can be subdivided using the Laurén classification
into 2 distinct histologic subtypes with different epidemiologic
and prognostic features (Fig. 54.2).7 The intestinal type of cancer
is characterized by the formation of gland-like tubular structures
with features reminiscent of intestinal glands. This type of gastric
cancer is more closely linked to environmental and dietary risk
factors,
The diffuse type of cancer lacks glandular
structure and consists of poorly cohesive cells that infiltrate the
wall of the stomach. It is found at the same frequency throughout
the world, occurs at a younger age, and is associated with a worse prognosis than the intestinal form
87
Extensive involvement
of the stomach by the diffuse type can result in a rigid and thickened
stomach, a condition referred to as linitis plastic
Adenocarcinoma of the stomach is also classified into proximal
tumors (EGJ and gastric cardia) and distal or nonjunctional
tumors (fundus, body, and antrum of the stomach
88
Junctional
cancers can be further classified according to the Siewert classification
by the location of the main tumor mass into
Type I (1 to 5
cm above the EGJ), Type II (from 1 cm above to 2 cm below the
junction), and Type III (2 to 5 cm below the junction) tumors
89
A common feature
of the initiation and progression to intestinal-type gastric cancer
is chronic inflammation oaf the gastric mucos
```
Risk Factors for Gastric Adenocarcinoma
DEFINITE
Adenomatous gastric polyps*
Chronic atrophic gastritis
Cigarette smoking
Dysplasia*
EBV
History of gastric surgery (esp. Billroth II)*
Hp infection
Intestinal metaplasia
GENETIC FACTORS
Family history of gastric cancer (first-degree relative)*
Familial adenomatous polyposis (with fundic gland polyps)*
Hereditary nonpolyposis colorectal cancer*
Juvenile polyposis*
Peutz-Jeghers syndrome*
PROBABLE
High salt intake
History of gastric ulcer
Obesity (adenocarcinoma of the cardia only)
Pernicious anemia*
Regular aspirin or other NSAID use (protective)
Snuff tobacco use
POSSIBLE
Diet high in nitrates
Heavy alcohol use
High ascorbate intake (protective)
High intake of fresh fruits and vegetables (protective)
Low socioeconomic status
Ménétrier disease
Statin use (protective)
QUESTIONABLE
High green tea consumption (protective)
Hyperplastic and fundic gland polyps
```
90
Although it is currently assumed that presence of intestinal
metaplasia is most likely to mark the point of no return, there
is even an effect of Hp eradication if advanced lesions are present
The natural history of chronic Hp infection includes 3 possible
outcomes34: (1) simple gastritis, where patients often remain
asymptomatic; (2) duodenal ulcer phenotype, which occurs in
10% to 15% of infected subjects; and (3) gastric ulcer/gastric
cancer phenotype
91
There is a general consensus that TP53 is the most commonly
mutated gene in gastric cancer (60% to 70% of gastric cancers)
and that mutations in Ras, APC, and Myc are rare
Chronic atrophic gastritis, which is defined as the loss of specialized
glandular tissue in its appropriate region of the stomach, is an
established morphologic change that occurs along the sequence
toward the development of gastric cancer.238 The presence of
atrophic gastritis has an annual incidence of progression to gastric
cancer of approximately 0.1% to 1.0%.
92
There are 2 forms of atrophic gastritis (see Chapter 52). The
more common is environmental multifocal atrophic gastritis,
which is associated with Hp infection and more likely to be associated
with metaplasia
The presence of Hp infection is associated
| with an approximately 10-fold increased risk of atrophic gastritis.
93
second form of atrophic gastritis, autoimmune metaplastic atrophic
gastritis, is associated with anti-parietal cell and intrinsic factor
antibodies. This form of atrophy is confined to the body and
fundus. Autoimmune metaplastic atrophic gastritis is associated
with pernicious anemia and an increased gastric cancer risk, albeit
not as high as that seen with Hp-induced MAG, owing most likely
to a lesser degree of inflammation
Intestinal metaplasia (IM) can be subdivided into 3 categories,
as classified by Filipe’s group.254 Type I (complete) IM contains
goblet cells that secrete sialomucins and mature, nonsecretory
absorptive cells. Type 1 IM is not a risk factor for gastric cancer.
Type II (incomplete) IM contains few if any absorptive cells,
columnar “intermediate” cells in various stages of differentiation
secreting neutral or acidic sialomucins, and goblet cells secreting
sialomucins and/or occasionally sulfomucins. Type III (incomplete)
is less differentiated than type II, with the intermediate
cells secreting mainly sulfomucins and the goblet cells secreting
sialo- and/or sulfomucins. Type II or III IM is associated with
an approximately 20-fold increased risk of gastric cancer.
94
Hyperplastic polyps are generally benign, often multiple, and are
typically observed in the setting of chronic inflammatory conditions
(e.g., chronic atrophic gastritis), pernicious anemia, chronic
antral gastritis, adjacent to ulcers and erosions, and especially at
sites of gastroenterostomies
In contrast to other polyps of the stomach, gastric adenomas
undergo malignant transformation at a high rate. When gastric
adenomas were followed by serial endoscopy with biopsy, progression
through dysplasia to carcinoma in situ developed within
4 years in approximately 11% of cases
95
management of gastric polyps.278 Among the
recommendations were: (1) all gastric polyps should be at least
biopsied; (2) all gastric adenomas, symptomatic polyps, and polyps
with dysplasia should be removed; and (3) Hp, if present,
should be eradicated in patients with hyperplastic or adenomatous
The Billroth II operation with gastrojejunostomy
predisposes to the development of cancer at a 4-fold higher rate
than a Billroth I procedure with gastroduodenostomy, suggesting
that bile reflux may be a significant predisposing factor
96
Gastric cancer is metastatic at the time of diagnosis in 33%
of cases
Early gastric cancers are asymptomatic in up to 80% of cases
When a nonhealing gastric
ulcer is found, at least 6 to 8 biopsy specimens from the edge
and base of the ulcer are recommended
97
American
Gastroenterological Association has recommended that an upper
endoscopy be performed in patients who are older than 55 years
with new-onset dyspepsia and in patients younger than 55 years
who have “alarm” symptoms (weight loss, recurrent vomiting,
dysphagia, evidence of bleeding, anemia
Dyspeptic patients
in whom an empirical trial of PPIs and eradication of Hp do not
relieve symptoms should undergo prompt endoscopic evaluation
as well.
98
polypoid (Ip and Is), nonpolypoid (IIa, IIb,
and IIc), nonpolypoid and excavated (III).
(From the Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon:
T1 tumors are confined to the mucosa
(T1a) and submucosa (T1b); T2 tumors invade the muscularis propria but not the serosa; T3 tumors penetrate
the subserosal connective tissue without involving the visceral peritoneum or contiguous structures; and T4
tumors invade the serosa (visceral peritoneum) and may involve adjacent organs and tissues
99
Accurate staging in gastric cancer is important for treatment
decisions. EUS is the best-studied modality for the staging of
gastric cancer and remains the test of choice for assessing tumor
depth and nodal involvement
EUS allows the visualization of the 5 layers of the gastric wall.
The superficial gastric mucosa is represented by an echogenic
first layer, and the deeper mucosa by a hypoechogenic second
layer; the submucosa is represented by an echogenic third layer,
the muscularis propria as a hypoechogenic fourth layer, and the serosa as an echogenic fifth layer.
100
There are data to suggest that large tumor size (>5 cm)
may be independently associated with worse survival, independent
of nodal status or overall tumor stage
Lesions larger than 4.5
cm have a greater than 50% chance of spread into the submucosa,
are associated with “positive” nodes, and are therefore less likely
to be endoscopically resectable
101
The following criteria have been suggested for EMR in gastric
cancer: (1) the cancer is located in the mucosa and the lymph
nodes are not involved, as indicated by EUS examination; (2) the
maximum size of the tumor is less than 2 cm when the lesion is
slightly elevated (type IIa) and less than 1 cm when the tumor is
flat or slightly depressed (type IIb or IIc) without an ulcer scar;
(3) there is no evidence of multiple gastric cancers or simultaneous
abdominal cancers; and (4) the cancer is of the intestinal
type.
Despite these guidelines, it is generally not possible to remove lesions larger than 1.5 to 2.0 cm en bloc by EMR, and piecemeal removal of EGC is associated with decreased rates of curative resection
The Japanese have developed expanded
criteria for ESD for early gastric cancer:
(1) mucosal intestinaltype cancer of any size without ulceration,
(2) mucosal intestinaltype cancer less than 3 cm with ulceration, and
(3) submucosal intestinal-type cancer less than 3 cm and with submucosal invasion less than 500 μm
102
Primary gastric lymphomas account for 5% of gastric neoplasms,
with an increasing trend worldwide.16 The stomach is the most
common extranodal site of lymphoma and accounts for 68% to
75% of PGILs.
GISTs comprise 1% to 3% of all malignant GI tumors; they are
| the most common mesenchymal tumor of the GI tract
103
A simplified “rule of 5s” has been advocated
in which size larger than 5 cm and more than 5 mitoses per 50
high-power fields (HPFs) define an intermediate-high risk gastric
GIST and in which size larger than 5 cm or more than 5 mitoses
per 50 HPFs define an intermediate-high risk nongastric GIST
```
Most GISTs (60% to 70%) arise in the stomach; 20% to
30% originate in the small intestine, and less than 10% in the
esophagus, colon, and rectum.
```
104
The second most common site for GISTs to arise is in the small intestine.
98,99
In one report, approximately half of all small bowel tumors
| identified on small bowel capsule endoscopy were GISTs
105
GISTs visualized by EUS appear as hypoechoic
masses contiguous with the fourth (muscularis propria) or second
(muscularis mucosae) layers of the normal gut wall. In one
study,115 7 the EUS features most predictive of so-called benign
GI GISTs were regular margins, tumor size 3 cm or less, and
a homogeneous echogenicity pattern.
Multivariate analysis
identified the presence of cystic spaces and irregular margins as
independent predictors of malignant potential. A second study
identified tumor size larger than 4 cm, irregular extraluminal
borders, echogenic foci larger than 3 mm, and cystic spaces
larger than 4 mm as factors that correlated with malignant
behavior in GIST.
106
TABLE 30.5 Comparison of Eosinophilic Esophagitis and GERD
EoE
Prevalence of atopy Very high
Prevalence of food sensitization
Involvement of proximal esophagus Yes
