Transcript The Stomach-Lecture 2

Anathomy
• The gastrointestinal tract possess
a broadly similar structure
throughout its length
- an innermost epithelium
- a subepithelial lamina propria
- two muscle layers, an inner
circular and an outer longitudinal
layer, between which lies the
myenteric plexus, the intrinsic
neural control system of the
musculature
• While this description most
accurately describes the small
intestine, the other organs of the
gastrointestinal tract differ only
subtly from this stereotype.
• The anatomy of the stomach
differs from the intestine,
possessing:
- an additional oblique muscular
layer
- at either end a sphincter—
specialized musculature designed
to act as a unidirectional valve to
control the flow of luminal
contents
• the sphincter between the
oesophagus and stomach (the
lower oesophageal sphincter) lies
at the level of the diaphragm
• the sphincter between the
stomach and small intestine is
known as the pylorus.
Proceeding from the surface
epithelium into the pits, the
mucosal cells considered in
detail in the following
subsections include the
following:
- mucous cells and
mucous neck cells, which line
the surface and extend into the
pits, respectively;
- parietal cells, which secrete
hydrochloric acid and intrinsic
factor;
- endocrine cells,
which secrete a variety of
mediators;
- toward the base of the pits,
chief cells, which secrete
pepsinogens
Mucous cells.
•The acid-secreting parietal cell is located in the
oxyntic gland, adjacent
to ECL cell, D cell, important in the
gastric secretory process
•This unique cell also secretes intrinsic factor (IF).
•The parietal cell expresses receptors for several
stimulants of acid secretion including histamine (H2),
gastrin (cholecystokininB/gastrin receptor), and
acetylcholine (muscarinic, M3)
-Each of these are G protein–linked
-Binding of histamine to the H2 receptor leads to
activation of adenylate cyclase and an increase in
cyclic AMP.
-Activation of the gastrin and muscarinic receptors
results in activation of the
proteinkinaseC/phosphoinositide signaling pathway.
-Each of these signaling pathways in turn regulates a
series of downstream kinase cascades, which control
the acid-secreting pump, H, K-ATPase.
•Parietal cells also express receptors for ligands that
inhibit acid production (prostaglandins,
somatostatin, and EGF).
•The duodenum (so
named because it is 12
fingers' breadth in
length)
•retroperitoneal
•possess on its medial
aspect the ampulla of
Vater which connects
the pancreatic and
common bile ducts to
the duodenal lumen
Duodenal juice
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an alkaline protein-containing fluid of
weak digestive power that is secreted by
the duodenum
contains invertase, maltase, lactase,
erepsin, and enterokinase
the chyme passes out of the stomach with
an acid reaction, and its undigested
constituents are at once subjected to a
second process of digestion in the
duodenum by an alkaline fluid, which is a
mixture of the pancreatic juice, the bile,
and the enteric juice.
the pancreatic juice converts the
remaining starch into sugars, and the
remaining proteids into peptones, leucin,
tyrosin, and fatty acids
the bile it partly emulsifies and partly
saponifies the fats
the sugars are converted into lactic acid
and butyric acid, possibly in part by the
succus entericus, which is also amylolytic.
Defensive mechanisms
• The properties of the surface epithelial cells that
provide the second line of gastroduodenal
defensive factors include restitution, epithelial
cell metabolism (e.g., transmembrane,
transcellular resistances), acid-base transporters
that maintain intracellular pH, and mucus
secretion.
• The key subepithelial process that prevents
mucosal injury is adequate mucosal blood flow.
Common symptoms
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Dyspepsia
Nausea
Vomiting
Bloating
Fast enough
Bloating
Indigestion
Pain in
Epigastric
Region
Patients may speak of:
• indigestion (to describe
any low-grade upper
abdominal discomfort)
• sickness (to describe
either nausea or
vomiting)
Dyspepsia
• upper abdominal or lower chest discomfort or pain
related to eating which may be described by the
patient as a burning, a heaviness, or an aching
• often accompanied by other symptoms such as
nausea, fullness in the upper abdomen, or belching
• the symptoms of upper gastrointestinal disease are
imprecise and non-specific - the clinical history will
often facilitate making the correct diagnosis quickly
and limit unnecessary investigation
Functional dyspepsia
• previously called non-ulcer dyspepsia
• dyspepsia "without evidence of an organic
disease that is likely to explain the symptoms“
• is estimated to affect about 15% of the
general population in western countries
Nausea
• the term nausea should be restricted to the
feeling of being about to vomit.
• acute nausea is usually accompanied by
hypersalivation.
• caused by labyrinthine stimulation (as in motion
sickness), distension of hollow viscera, or any
severe somatic pain and by some drugs,
especially opiates and those used in
chemotherapy for malignant conditions
Vomiting
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forceful ejection of gastric contents through the mouth by the co-ordinated
contraction of abdominal and gastric muscles with relaxation of the lower
oesophageal sphincter.
non-productive vomiting is called retching.
Vomiting occurs with peptic ulceration, especially when there is delayed gastric
emptying (pyloric stenosis), and with advanced gastric cancer.
It occurs with disorders of the biliary tree (especially as a result of gallstones) and
with acute pancreatitis (in which it is a prime symptom).
It is an important symptom of intestinal obstruction, especially with lesions above
the ileocaecal valve, and it may occur with any cause of peritoneal inflammation
such as appendicitis.
Metabolic causes of vomiting include diabetic ketoacidosis, hypoadrenalism, and
uraemia.
Drugs which cause vomiting include opiates, some antibiotics (for example
erythromycin), and chemotherapeutic agents.
Alcoholism, raised intracranial pressure, and pregnancy are important causes of
early morning vomiting.
Effortless vomiting
• without a definable cause may be psychogenic
- this is usually a disorder of young women many of
whom have suffered psychological trauma (such as
sexual abuse)
- it is not related to the vomiting of bulimia, a condition
that is part of the anorexia nervosa syndrome
• Rumination is the repetitive regurgitation of gastric
contents into the mouth after meals, the regurgitated
material then being reswallowed. It is not associated
with nausea, heartburn, or discomfort and often
appears to be simply an acquired habit.
Abdominal pain
• Pain in the upper abdomen has been considered under
the heading dyspepsia. Upper abdominal discomfort is
so common that its presence alone is of no value in
distinguishing between those patients with organic
disease and those with a functional disorder.
• Symptoms are rarely specific but should be
reinterpreted in the light of screening investigations
(such as the blood count, a straight radiograph of the
abdomen, and assessment of serum markers of
inflammatory disease).
Investigations
• Upper GI endoscopy
• Investigation for Helicobacter pylori
• Find medication-related dyspepsia
PEPTIC ULCER
•A gastrointestinal ulcer is
defined as a breach in the
epithelium that penetrates the
muscularis mucosae.
•If the muscularis is not
breached it is called an erosion.
•Duodenal ulcers and gastric
ulcers are often considered
together as peptic ulcers but
differ considerably with regard
to epidemiology, pathogenesis,
presentation, and
management
Epidemiology
• Developed countries: 1980-1999
– DU 8-10% and annual incidence of 0,2%
– GU 3 times more rare
– Decrease in incidence since 1970
– Decrease of DU principally in men M/F 3-4/1 la
2/1 and even 1/1
– GU no significant modifications in incidence.
– Decreased incidence principally in young and
middle aged men; is becoming a disease of old
age.
International prevalence (Place)
Etiopathogenesis
• Aggressive factors implicated in ulcer
– Acid hypersecretion
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Increase in parietal cell mass
Increase in vagus tone
Increase in parietal cellular sensibility to gastrin
Antral G cells hyper function
Nocturnal acid hypersecretion
Deterioration in inhibitory mechanism of acid secretions
Motility disturbances: Duodenal ulcer-rapid gastric emptying,
gastric ulcer- gastric hypomotility
– Pepsin hypersecretion
• Hiperpepsinogenemia I
- Helicobacter pylori
– Duodenogastric reflux
• Biliary acids, lisolecitin and proteolytic enzymes.
Etiopathogenesis
• Factors of defense
– Pre-epithelial factors
• Bicarbonate and mucus barriers
• Tensioactive phospholipids
– Epithelial factors
• Cellular resistance (normal cellular metabolism)
• Intra-cellular PH maintenance
• Growth factors (epithelial growth factors,
Prostaglandins, NO)
• Mechanism of repair of epithelial lesions
– Post-epithelial factors
• Abnormal mucous blood flow
Etiopathogenesis
• Individual factors
– Genetic factors: group 0 & A, Lewis and nonsecretory factor (a-b-)
– Familial Hyperpepsinogenemia type I
– Studies: 39% genetic factors and 61% average
predisposing factors
– Associated diseases : ZE syndrome, MEN I,
systemic mastocytosis, alfa 1 antitrypsin
deficiency, hepatic cirrhosis, chronic pancreatitis,
Crohn’s disease, COPD, polycythemia vera,
basophilic leukemia, amyloidosis
– Personality changes : anxiety, neuralgia
Etiopathogenesis
• Average risk
factors
– smoking
– NSAID
– Corticotherapy
( controversial)
– Stress
Ulcerous disease
• chronic disease with
multiple complain
(dyspeptic syndrome)
characterized anatomopathologically by the
presence of ulcerous
crater which crosses the
muscularis mucosa,
with gastric and /or
duodenal localization
Etiology/Classification
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Helicobacter Pylori + ulcer
NSAID (aspirin) induced ulcer
Stress induced ulcer
Ulcer which accompanies genetic diseases and
syndromes
• Helicobacter pylory - ulcer.
How it happens …
• Peptic ulcers happen when the acids that help
you digest food, damage the walls of the
stomach or duodenum.
• The most common cause is infection with a
bacterium called Helicobacter pylori.
• Another cause is the long-term use of
nonsteroidal anti-inflammatory medicines
(NSAIDs) such as aspirin and ibuprofen.
• Stress and spicy foods do not cause ulcers, but
can make them worse.
Gastric ulcers
• GUs tend to occur later in life than duodenal
lesions, with a peak incidence reported in the
sixth decade.
• More than half of GUs occur in males and are
less common than DUs, perhaps due to the
higher likelihood of GUs being silent and
presenting only after a complication develops.
• Autopsy studies suggest a similar incidence of
DUs and GUs.
Gastric ulcer
• can represent a malignancy.
• Benign GUs are most often found distal to the junction
between the antrum and the acid secretory mucosa. This
junction is variable, but in general the antral mucosa
extends about two-thirds of the distance of the lesser
curvature and one-third the way up the greater curvature.
• Benign GUs are quite rare in the gastric fundus and are
histologically similar to DUs. Benign GUs associated with H.
pylori are associated with antral gastritis.
• In contrast, NSAID-related GUs are not accompanied by
chronic active gastritis but may instead have evidence of a
chemical gastropathy.
Gastric ulcer
• the majority of GUs can be attributed to either H.
pylori or NSAID-induced mucosal damage.
• GUs that occur in the prepyloric area or those in
the body associated with a DU or a duodenal scar
are similar in pathogenesis to DUs.
• Gastric acid output (basal and stimulated) tends
to be normal or decreased in GU patients.
• When GUs develop in the presence of minimal
acid levels, impairment of mucosal defense
factors may be present.
Macroscopic – gastric ulcer
Microscopic – gastric ulcer
Duodenal ulcer
• DUs are estimated to occur in 6 to
• 15% of the western population. The incidence
of DUs declined steadily
• from 1960 to 1980 and has remained stable
since then. The death rates,
• need for surgery, and physician visits have
decreased by 50% over
• the past 30 years.
Duodenal ulcer pathology
• DUs occur most often in the first portion
• of duodenum (95%), with 90% located within 3 cm of the
pylorus.
• They are usually 1 cm in diameter but can occasionally
reach 3 to
• 6 cm (giant ulcer). Ulcers are sharply demarcated, with
depth at times
• reaching the muscularis propria. The base of the ulcer often
consists
• of a zone of eosinophilic necrosis with surrounding fibrosis.
Malignant
• duodenal ulcers are extremely rare.
Duodenal ulcer
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Many acid secretory abnormalities have been described
in DU patients. Of these, average basal and nocturnal gastric
acid secretion appear to be increased in DU patients as compared to
control; however, the level of overlap between DU patients and control
subjects is substantial. The reason for this altered secretory process is
unclear, but H. pylori infection may contribute to this finding. Accelerated
gastric emptying of liquids has been noted in some DU patients
but is not consistently observed; its role in DU formation, if any, is
unclear. Bicarbonate secretion is significantly decreased in the duodenal
bulb of patients with an active DU as compared to control subjects.
H. pylori infection may also play a role in this process.
Macroscopic –duodenal ulcer
A 49-year-old man was admitted with sudden onset of severe pain in the
epigastrium. Recently, he had taken a course of a non-steroidal antiinflammatory drug (NSAID). This had caused indigestion, which had
worsened in the two days prior to his presentation. On examination, the
patient was ill and had a rigid abdomen. The operative photograph
shows a perforated duodenal ulcer.
Microscopic – duodenal ulcer
• Representative
micrographs of
duodenal mucosa
stained by haematoxylin
and eosin
Ulcer HP+
• 80-90% of ulcers after excluding AINS
• Increased risk 4x duodenal ulcer and 3x gastric
ulcer
• Decreased risk of recurence if eradication is
successful: 6% 1 yr and 17% > 1 yr, superior
supraselective vagotomy.
UK Incidence & Prevalence (Person)
H. pylori infection
• Incidence: 1-3% of adults p.a. (HPA)
• Prevalence infection: 40% population (HPA: >50% of 50+yr
olds)
Ulceration
•Incidence:
–DU in 30-50yrs old; higher incidence in men
–GU in >60yr olds; higher incidence in women
•Low prevalence in younger age groups
•Duodenal ulcer: up to 10% of population
Ulcer HP+
• Reversible gastrine hypersecretion
predominant postprandial
• Increase in acid secretion if gastritis is antral
• Hipersecretion of pepsinogen
• Changes in adherent mucus
• Changes in appearance of gastroduodenal
mucus.
Ulcer induced by NSAIDs
• Mucus, bicarbonate secretion, microcirculation
(mucosal appearance depends upon PG (PGE)
• NSAIDs inhibits COX1 and COX2 by decreasing
physiological and pathological prostaglandins
(systemic effect )
• Some of NSAID (weak acids) have mucosal irritant
effect (local effect )
• NSAID and HP are independent factors in
ulcerogenesis but have additional effects (to
eradicate HP before starting treatment with
NSAID)
• Mucosal adaptation
Ulcer induced by NSAIDs
• Injury to the mucosa also occurs as a result of the
topical encounter
• with NSAIDs. Aspirin and many NSAIDs are weak acids
that remain
• in a nonionized lipophilic form when found within the
acid environment
• of the stomach. Under these conditions, NSAIDs
migrate across
• lipid membranes of epithelial cells, leading to cell
injury once trapped
• intracellularly in an ionized form.
Endocrine Ulcer
• Zollinger Ellison Syndrome (gastrinoma) isolated
or in association with MEN I (0,5%)
Stress Ulcer
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Acid hypersecretion
Systemic arterial hypotension
Stress coagulopathy
Ischemic induced mucosal defects.
Clinical manifestations of ulcer disease
Symptoms
Epigastric pain described as a burning or gnawing discomfort can
be present in both DU and GU.
GU
• Discomfort may actually be
precipitated by food.
• Nausea and weight loss
occur more commonly in
GU patients.
DU
• The typical pain pattern in
DU occurs 90 min to 3 h
after a meal and is
frequently relieved by
antacids or food.
• Pain that awakes the
patient from
sleep(between midnight
and 3 A.M.) is the most
discriminating symptom
The mechanism for development of abdominal pain in ulcer patients is unknown. Several
possible explanations include acid-induced activation of chemical receptors in the duodenum,
enhanced duodenal sensitivity to bile acids and pepsin, or altered gastroduodenal motility.
Diagnosis
• Endoscopy (>40yrs, first time). Capture all cases?
• Faecal / breath tests for H. pylori
• GI X-ray
False positive tests
Missed cases? – risk of transmission / disease progression
Why are they important?
• HPA – “infectious disease” but main effects are from chronic
burden
• Potential “medical emergency”
• Chronic symptoms – health and economic costs
• H. pylori also linked to:
– Functional dypepsia
– Cancer (2-6x more likely, though still rare)
• Differential clinical outcome - interaction between bacterial
properties (phenotypic variation), genetics and environmental
/ behavioural factors
Emergency admission
for perforation
Rates per million
resident population.
Three-year moving
averages
Implications for care
of older people
(Bardhan et al. 2004, Digestive
& Liver Disease 36(9), 577588)
Endoscopy
• endoscopy provides the most sensitive and
specific approach for examining the upper
gastrointestinal tract
• facilitates photographic documentation of a
mucosal defect and tissue biopsy to rule out
malignancy (GU) or H. pylori
• endoscopic examination is particularly helpful in
identifying lesions too small to detect by
radiographic examination, for evaluation of
atypical radiographic abnormalities, or to
determine if an ulcer is a source of blood loss.
• Endoscope is passed through the mouth, to
the stomach, examining the lining of the
stomach
• Many endoscopes are equipped with a
small clipper with which tissue samples can
be taken (endoscopic biopsy)
• Endoscopes can also be used for treatment.
Endoscopy
Endoscopy
Benign gastric ulcer
Benign gastric ulcer
Endoscopy:
Duodenal ulcer
Duodenal ulcer (a)
Duodenal ulcer (b)
Radiographic (barium study)
• still commonly used as a first test for documenting an ulcer
• the sensitivity of older single-contrast barium meals for detecting a DU is
as high as 80%, with a double-contrast study providing detection rates as
high as 90%
• sensitivity for detection is decreased in small ulcers (0.5 cm), presence of
previous scarring, or in postoperative patients
• DU appears as a well-demarcated crater, most often seen in the bulb
• GU may represent benign or malignant disease
• typically, a benign GU also appears as a discrete crater with radiating
mucosal folds originating from the ulcer margin
• ulcers 3 cm in size or those associated with a mass are more often
malignant
• up to 8% of Gus that appear to be benign by radiographic appearance
are malignant by endoscopy or surgery. Radiographic studies that show a
GU must be followed by endoscopy and biopsy.
Typical radiographic features of benign gastric ulcer (a)
Typical radiographic features of benign gastric ulcer (c)
Typical radiographic features of benign gastric ulcer (d)
Typical radiographic features of duodenal ulcer (b)
Diagnosis of H. pylori infection
• Three methods can be used to detect H. pylori in gastric biopsies:
1. The biopsy urease test depends on the the ability of the bacterium to
generate alkali.
2. H. pylori bacteria are readily detected histiologically using special stains.
3. Bacterial culture allows the antibiotic sensitivity of the patient's strain to
be determined.
• Two tests allow H. pylori to be diagnosed without endoscopy:
1. Serology is accurate and convenient but remains positive for several
months after successful eradication, and is not useful for determining
whether eradication has been successful.
2. The urea breath test. The patient drinks a solution of urea containing
carbon atoms labelled with 13C or 14C. Labelled CO2, generated by
bacterial urease, can be detected in the breath by mass spectroscopy or
radioactive counting if the infection is present. This test is ideal for testing
the success of eradication, if this is required.
Prognosis
• Recurrence of H. pylori-related duodenal ulceration is
uncommon after successful eradication.
• The rate of reinfection with H. pylori is about 0.7 per cent
per annum in Western adults. Higher rates of reinfection
have been reported in developing countries but this is not
universal and the reinfection rate is 1 per cent per annum
in China. Apparent reinfection in the West is often actually
persistence of the initial infection.
• Recurrent ulceration in the absence of H. pylori may be
due to NSAIDs, Crohn's disease, or the Zollinger–Ellison
syndrome. In some patients recurrent ulceration after
eradication of H. pylori is associated with persistent high
acid output in the absence of a gastrinoma.
COMPLICATIONS
• Acute:
– bleeding (hematemesis, melena)
– perforations
• Chronic:
– piloric stenosis
– Cancer??????????
Gastrointestinal bleeding
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Haemorrhage remains a challenging problem and is the main cause of death from
peptic ulcers.
Blood loss may be slow and present as unexplained anaemia but more typically
presents acutely with haematemesis or melaena or both with varying degrees of
hypovolaemic shock.
Older patients need particular attention because they are much more vulnerable
to the effects of hypovolaemia.
Endoscopy is performed, preferably after the patient's condition has stabilized, to
define the source of bleeding and to apply endoscopic treatments. Ulcers which
are actively bleeding or show stigmata, such as adherent clot or a visible vessel,
which make further bleeding likely can be treated with lasers, heater probes, or
local injection of adrenaline.
Rebleeding is an indication for surgery.
After the acute episode, it is important to attend to the cause of the ulcer.
Eradication of H. pylori, if it is present, greatly diminishes the frequency of further
episodes of bleeding in future, but this is a measure that is frequently overlooked.
Hematemesis
• "hema“ - blood + "emesis“ - vomit = bloody
vomit
• red
• coffee ground vomitus - occurs when blood is
in contact with gastric acid for at least 1 hour.
Hematemesis/Hemoptisis
Where is it from?
GI TRACT
RESPIRATORY TRACT
Dark red or brown
In clumps
Mixed with food
Acidic pH
Stomachache, abdominal discomfort
Nausea, retching before and after episode
Bright red
Foamy, runny
Mixed with mucous
Alkaline pH
Chest pain, warmth or gurgling over the
chest
Persistent cough
Melena
• the passage of dark black, liquid, tarry,
metallic-smelling stools
• melenic stools usually indicate bleeding
proximal to the right side of the colon
• it usually indicates that hemorrhage has
remained for > 8hrs in the GI tract
Hematochesis
• the passage of bright red stools
• is usually indicative of bleeding from the
rectum & anus, however 50% are due to
proximal lesions (mainly in the colon) that are
profuse enough that they avoid remaining in
the gut for 8hrs & are not expressed as blood
intermixed with stools
Causes of GI bleeding
• duodenal ulcer hemorrhage (25%)
• gastric ulcer hemorrhage (20%)
• mucosal tears of the esophagus or fundus
(Mallory-Weiss tear)
• esophageal varices
• erosive gastritis, erosive esophagitis
• Dieulafoy lesion
• gastric varices
• gastric cancer
• ulcerated gastric leiomyoma
Upper gastrointestinal bleeding
Stigmata of recent hemorrhage (a)
Stigmata of recent hemorrhage (b)
Stigmata of recent hemorrhage (c)
Stigmata of recent hemorrhage (d)
Stigmata of recent hemorrhage (e)
Stigmata of recent hemorrhage (f)
Stigmata of recent hemorrhage (g)
Stigmata of recent hemorrhage (h)
Penetration
• sudden onset or worsening of pain with considerable
abdominal tenderness followed by the onset of peritonitis
with board-like rigidity, rebound tenderness, and loss of
bowel sounds
• gas in the peritoneum may lead to loss of liver dullness to
percussion, and is usually visible beneath the diaphragm on
erect chest radiograph
• the differential diagnosis includes acute
pancreatitis,
acute cholecystitis and other causes of an acute abdomen
such as gut infarction or perforation of other organs
Perforated peptic ulcer
Acute peritoneal syndrome
Pyloric stenosis
• repeated duodenal ulceration
• the main symptom is vomiting which may contain food
eaten the previous day
• typical symptoms of duodenal ulceration may or may not
precede the onset of vomiting
• patients rapidly become dehydrated and develop
hypokalaemia with a metabolic acidosis, they may also be
malnourished
• a succussion splash, which is normally present up to 4 h
after a meal, is present at other times
• barium radiology or upper endoscopy show a distended
stomach containing retained food and secretions and with
a narrowed pyloric canal
• the differential diagnosis includes cancer of the distal
stomach
Pyloric outlet obstruction and peripyloric ulcer disease (b)
Pyloric outlet obstruction and peripyloric ulcer disease (c)
Pyloric outlet obstruction and peripyloric ulcer disease (d)
Piloric stenosis – Investigations
Piloric stenosis
Differential diagnosis
• Nonulcer Dyspepsia =abdominal pain or discomfort that
occurs in the upper abdomen without the presence of an
ulcer, is a major complaint that affects about 15% of the
population annually, most of whom do not seek medical
care
• Other Gastrointestinal Diseases GI diseases that mimic
PUD include upper GI neoplasms (i.e., gastric and
pancreatic cancer), mesenteric ischemia, which is
sometimes referred to as abdominal angina, and
pancreatitis or cholecystitis. Gastric or duodenal
involvement with Crohn’s disease or with typical and
atypical strains of Mycobacterium tuberculosis can
produce gastric retention and ulcer-type symptoms
STOMACH CANCER
Epidemiology
– More common in man
than in women
– More frequent in China,
Japan, Chile, former
USSR, Est Europe; low in
India, Africa
– Dramatic decline in
incidence in past 20-30
years
Incidence
• gastric cancer is the second most common cause
of cancer mortality, after lung cancer,
worldwide. It is estimated that gastric cancer
causes more than 620,000 deaths per year
worldwide. In the United States, approximately
21,500 new cases of gastric cancer were
diagnosed in 2000 and 13,000 patients died of
this disease the same year.
• most gastric tumors are adenocarcinomas
• other less common gastric malignant diseases:
lymphoma, stromal tumor and gastric polyps
Malignant gastric neoplasms
Risc factors
– diet: high carbohidrates and salt preserved foods,
deficiet in fruits and vegetable
– high dietary intake of nitrates (preservation food)
– Helicobacter pylori
– atrophic gastritis (pernitious anemia)
– partial gastrectomy (more than 15 years)
Patological features
• Adenocarcinoma accounts for 95% of the
stomach cancers, whereas squamous cell
carcinoma, carcinoid tumors, leiomyosarcoma,
and lymphoma constitute the rest of the
gastric tumors.
Macroscopic
• gastric cancers can be broadly categorized by their location and
appearances
• proximal (cardia) versus distal (including body and antrum) cancers major etiologic significance
- distal cancers are more common in areas with a high gastric cancer
incidence
- cardia cancers are more prevalent in whites from populations with
a low background incidence of gastric cancer
• the former may be closely related to chronic H pylori infection,
whereas the latter is often the consequence of chronic
gastroesophageal reflux disease and Barrett esophagus
• the incidence of gastroesophageal junction carcinomas is
increasing in the United States 4 and in many other developed
countries
There are several different forms of gastric cancer; this slide shows an infiltrating type. Here, malignant cells in
groups or lines tend to infiltrate the wall of the stomach, causing it to become thicker, and rigid. It comes to
resemble a “leather bottle” used to carry wine. It is also known as linitis plastica (linitis originally referred to linen or
cloth) and this was thought to be due to inflammation (“itis”), but the inflammatory-appearing cells have been
shown to be cancer cells. Mucin stains are sometimes helpful in differentiating cancer cells from chronic
inflammatory cells.
Microscopic
• Microscopically, several histological classifications of gastric cancer are
used.
• The most widely used classification, proposed by Lauren, 87 broadly
divides gastric cancer into diffuse and intestinal types, with contrasting
epidemiology, etiology, and prognosis
• The intestinal type is characterized by cohesive neoplastic cells forming
glandular tubular structures, is more common in the distal stomach and is
often preceded by preneoplastic stages such as intestinal metaplasia. It is
more prevalent in regions with a high background incidence of gastric
cancer and is generally associated with a better surgical outcome than the
diffuse type
• The diffuse type is characterized by its biologic behavior, shows sheets of
epithelial cells or cells scattered in a stromal matrix without evidence of
gland formation; may contain signet-ring cells.
• Approximately 5% to 10% of tumors remain unclassified, and they are
called mixed-type tumors
Cascade of gastric carcinogenesis
• Based on extensive
observational studies in
populations with high gastric
cancer incidences, gastric
cancer is generally believed to
be a multistep progression
from chronic gastritis,
atrophy, and intestinal
metaplasia ultimately to
dysplasia and cancer.
• This paradigm of gastric
carcinogenesis has been
coined the Correa cascade,
which was subsequently
modified to incorporate H
pylori in the initial stage of the
sequence.
H&E appearance of intestinal type gastric cancer.
H&E appearance of diffuse type gastric cancer.
Symptoms
• Early gastric cancer typically produces no symptoms. Only patients with
advanced disease will notice any discomfort.
-
-
The most frequent symptoms and signs patients experience are weight
loss and abdominal pain.
Persistent vomiting can occur in antral tumors obstructing the gastric
outlet.
Dysphagia may be present when tumors obstruct the gastroesophageal
junction.
Early satiety, although not a common presentation of gastric cancer, may
suggest a diffusely infiltrative tumor resulting in loss of distensibility of the
stomach.
Gastrointestinal bleeding has been reported in about 10% to 15% of
patients, but frank bleeding is rare. Overt massive upper gastrointestinal
bleeding may be more common in gastric stromal tumors.
Signs
• Physical signs are usually absent in patients with gastric carcinomas,
except in metastatic disease.
• A palpable abdominal mass is rare before regional extension of
the tumor.
• Metastasis to the left supraclavicular lymph node produces the socalled Virchow node, along the peritoneal surfaces may result in a
periumbilical nodule ( Sister Mary Joseph node), ovarian mass (
Krukenberg tumor), or tumor mass in the cul-de-sac ( Blumer
shelf); peritoneal seeding of tumor may produce malignant ascites
• Paraneoplastic syndromes: acanthosis nigricans, membranous
glomerulonephritis, microangiographic hemolytic anemia, arterial
and venous thrombi (Trousseau syndrome), seborrheic dermatitis (
Leser-Trélat sign) and dermatomyositis.
Diagnosis
• Because of the silent nature of the disease, timely diagnosis of gastric
cancer is difficult.
• Conventionally, radiologic imaging played a major role in the initial
diagnosis of gastric cancer; with the use of double-contrast techniques false-negative rates of up to 25% have been reported in lesions between 5
and 10 mm in diameter
• Upper gastrointestinal endoscopy and biopsy have been the standards for
the diagnosis of gastric cancer
• CT scanning defines the spread of the primary tumour and gross
lymphatic and metastatic disease
• MRI scanning
• Endoscopic ultrasound is useful in the local staging of gastric carcinoma.
• Laparoscopy may be necessary to confirm the presence of peritoneal
metastases
• Ultrasonography will identify hepatic metastases
• Biochemical markers
Biochemical markers
• low serum pepsinogen I
• elevated gastrin level
• H. pylori antibody testing
Laboratory
anemia -iron deficiency
hypoalbuminemia- poor nutrition
abnormal liver chemistry - hepatic involvement
STAGING
• The clinical and pathological
staging of gastric carcinoma is
of paramount importance in
the management of the
patient.
• The depth of the tumor
invasion (T), the involvement
of lymph nodes (N), and the
presence of metastasis to
other organs (M) are the
major considerations.
• This TNM staging system has
been extensively used in the
evaluation of gastric cancer.
Radiological findings
• It may not be possible to
differentiate a benign from a
malignant ulcer by barium studies
• A malignant ulcer typically has an
asymmetric ulcer crater
excentrically located in an
irregular mass with distortion or
obliteration of the normal
mucosal fold surrounding the
ulcer.
• Other features such as nodularity,
clubbing, fusion, or amputation of
radiating folds also suggested
malignancy.
• The use of radiologic imaging has
gradually been replaced by
endoscopy.
Endoscopy
• Endoscopy is widely used in the initial
diagnosis of gastric cancer and has generally
replaced contrast radiologic studies in many
centers.
Gastric carcinoma
Endoscopic view reveals presence of obviously ulcerated mass
CT
• (CT) scanning in the preoperative staging, its
value remains disputable.
• One of the limitations of CT is the inability to
differentiate between different layers of the
gastric wall and hence the inability to define
the T stage.
• The role of CT is confined to its ability to
demonstrate invasion outside the stomach
wall and the presence of distant metastasis.
MRI
• The role of magnetic resonance imaging (MRI) in the
preoperative staging of gastric cancer is yet to be
defined.
• MRI requires a longer scan time than CT and thus is
easily subjected to artifact from respiration and bowel
movement. The other limitation of MRI is the lack of a
widely accepted oral contrast medium to distend the
stomach.
• MRI is superior to CT in delineating the layered
structure of the stomach wall, and it may be used in
predicting the depth of tumor invasion (T staging).
Nuclear Medicine
87 year old woman with neoplastic meningitis from gastric cancer.
FDG PET showed deoxyglucose uptake in the stomach and the head of the pancreas (A).
No deoxyglucose uptake was apparent in the spinal canal on FDG PET (B).
Endoscopic ultrasonography (EUS)
• EUS provides an accurate assessment of T staging
and is superior to other imaging modalities for
the local staging of gastric cancer.
• The overall accuracy of EUS in T staging was
estimated to be 78%. 152 The accuracy tends to
be lower for T2 tumors because of the tendency
to overstage these tumors as a result of poor
differentiation between inflammation and
infiltration.
• The overall accuracy of N staging was estimated
to be 70%.
Endoscopic ultrasound confirms the depth of invasion
Carcinoma in the body of the stomach
Laparoscopy
• Often detects unexpected peritoneal or liver
metastasis that may not be identified by other
imaging techniques.
• The role of laparoscopy in preoperative staging is
difficult to evaluate because most published series
involved heterogeneous patient populations and
gave inconsistent results.
• The overall rate of detecting peritoneal and liver
metastases by laparoscopy ranged from 3% to 37%
and 2% to 25%, respectively
Prognostic
• The mortality of gastric cancer in many parts
of the world, with the exception of Japan, has
not been changed over the past few decades.
• A review from the National Cancer Data Base
revealed that the overall 5-year and 10-year
survival rates of patients diagnosed with
gastric cancer between 1985 and 1996 were
28% and 20%, respectively
• Men had a poorer prognosis than women
• Proximal cancer was associated with worse
prognosis than distal cancer
GASTRIC TUMORS OTHER THAN
ADENOCARCINOMAS
• Gastric Lymphoma
• Gastrointestinal Stromal Cell Tumors
• Gastric Carcinoid Tumors
GASTRIC POLYPS
Gastric Lymphoma
• Although primary gastric lymphoma is a rare malignant
disease that accounts for less than 5% of all gastric
malignancies, it is the most common form of
gastrointestinal lymphoma.
• It is estimated that approximately 70% of primary
extranodal lymphomas of the gastrointestinal tract arise
from the stomach.
• Most (80%) of gastric lymphomas are B cell in origin.
• The origin of this disease remains elusive, but many of
these tumors, particularly mucosa-associated lymphoid
tissue (MALT) lymphoma, are related to chronic
inflammation attributed to H pylori infection. H heilmannii
has also been linked to MALT lymphoma
Gastric Lymphoma
• Macroscopically, it may not be possible to differentiate
gastric lymphoma from carcinoma.
• Gastric lymphoma can be polypoid, fungating,
infiltrating, or even ulcerative in appearance. Most
lymphoma spreads by submucosal infiltration, and the
muscular layer is usually spared until a very late stage
of the disease. Further spread to local and regional
lymph nodes then follows.
• Microscopically, there is considerable heterogeneity
among different classification systems.
Gastric Lymphoma
• Symptoms of gastric lymphoma are nonspecific:
the most frequent symptoms are abdominal pain,
weight loss, nausea, vomiting, and anorexia.
Bleeding occurs in about 20% of cases.
• Upper gastrointestinal endoscopy is widely used
in the diagnosis of gastric lymphoma that can
provide histological proof.
• Multiple and deep gastric biopsies are usually
required for histological diagnosis because
tumors may develop in the submucosal lymphoid
tissue covered by normal gastric mucosa.
Gastric lymphoma-prognosis
• The grading and staging of gastric lymphoma are
the two decisive prognostic factors. In a review by
the German-Austrian Gastrointestinal Lymphoma
Study Group, the overall 2-year survival rates for
low-grade lymphoma ranged from 89% to 96%.
• Patients with high-grade lymphoma fare much
worse.
• When surgery was performed, patients with
complete resection had significantly better
survival than those with incomplete resection (2year survival of 83% to 88% versus 53%).
Mucosa-Associated Lymphoid Tissue
Lymphoma
• MALT lymphoma was first described in 1983 by Issacson and Wright 203
as a distinct pathological entity.
• They described that certain low-grade B-cell gastrointestinal
lymphomas recapitulated the features of Peyer patches or MALT.
• MALT lymphoma is characterized by the presence of plasma cells,
reactive follicles, and centrocyte-like cells that tend to invade mucosal
epithelium and form characteristic lymphoepithelial lesions.
• Most are of B-cell origin, and the most frequent site of involvement is
the stomach. These tumors tend to arise as polyclonal proliferation in
chronic inflammatory tissues, either autoimmune or infectious
Gastrointestinal Stromal Cell Tumors
• Gastrointestinal stromal tumors (GISTs) encompass a heterogenous
group of mesenchymal tumors
• Gastric stromal tumors with predominant smooth muscle
differentiation are termed gastric smooth muscle were
conventionally called leiomyomas and leiomyosarcomas.
• Gastric mesenchymal tumors of neural origin can be divided into
four main groups depending on the origin: peripheral nerve
(schwannoma, neurofibroma, and neuroma); sympathetic or
chromaffin system (neuroblastoma, ganglioneuroma, and
paraganglioma); gastrointestinal plexus (gastrointestinal autonomic
nerve tumor) and undetermined.
• The precise cellular origin of GISTs has been proposed to be the
interstitial cell of Cajal, an intestinal pacemaker cell
Gastrointestinal Stromal Cell Tumors
• Histologically, the distinction between benign and
malignant tumors is difficult, and there is no
unequivocal criterion to differentiate the two.
• Mitotic activity and tumor size appear to be more
reliable in categorizing tumors as benign, borderline,
and malignant, but there is no agreed cutoff point for
these values.
• The use of EUS may also help in differentiating benign
from malignant tumors.
• Tumors less than 30 mm in diameter with regular
margins and with a homogenous echo pattern are
usually benign.
Gastrointestinal Stromal Cell Tumors
• Patients can present with nausea, vomiting,
abdominal pain, gastrointestinal bleeding, and
even metastatic diseases.
• Bleeding is considered the most common
presentation.
• Malignant tumors can metastasize to the liver
and peritoneum and, rarely, to lymph nodes,
bone, and lung.
• Accurate preoperative diagnosis can be difficult,
and percutaneous biopsy carries a theoretical
risk of peritoneal seeding and tumor rupture.
Gastric Carcinoid Tumors
• Gastric carcinoid tumors are rare, accounting for only
about 3% of all carcinoids.
• Enterochromaffin-like cells are the main endocrine cell
types in type 1 and type 2 disease
• Type 1 tumors tend to be small (<100 mm) and
multiple. They are considered the most benign of the
three forms of carcinoid tumors and have a relatively
low frequency of metastasis, between 9% and 23%.
• Type 2 tumor is associated with the gastrin-producing
neoplasms in Zollinger-Ellison syndrome as part of the
multiple endocrine neoplasia syndrome type I. This
type of carcinoid has intermediate metastatic potential
Gastric Carcinoid Tumors
• The clinical presentations of gastric carcinoids are
usually nonspecific and variable including pain,
vomiting, anemia, and bleeding, or they can be
discoveredincidentally during endoscopy for
other reasons.
• Presentation with the typical carcinoid syndrome
of flushing, diarrhea, cutaneous edema, and
bronchoconstriction is uncommon.
• This is more closely related to the secretion of
histamine than to that of substance P, serotonin,
or 5-hydroxyindoleacetic acid.
Gastric Carcinoid Tumors-prognosis
• The overall 5-year survival in patients with all
types is 49%. However, patients with type 3
gastric carcinoids have a significantly worse
prognosis than do those with type 1 and 2
lesions.
• Five-year survival of patients with localized
gastric carcinoid is 64.3%, whereas survival in
patients with distant metastases drops to
10%.
Gastric polyps
• uncommon
• the estimated incidence is less than 1% in autopsy or
radiologic surveys
• up to 50% of gastric polyps are discovered
• incidentally during endoscopy for unrelated symptoms
• they may be solitary or multiple
• occasionally they are associated with other polyposis
syndromes (familial adenomatous polyposis, PeutzJeghers syndrome, Cowden syndrome, and CronkhiteCanada syndrome)
Gastric polyps
• One of the most important characteristics of
gastric polyps is the potential for malignant
transformation, particularly in adenomatous
polyps.
• It is believed that the histological composition
and size of the polyps may determine their
malignant potential.
• The frequency of malignant transformation
varies from 6% to 75% in the literature.
Adenomatous polyps
• Adenomatous polyps account for about 10%
of gastric polyps and they are more prevalent
in areas with a high incidence of gastric
cancer.
• This type of polyp is associated with a higher
risk of malignant transformation, and the risk
is size dependent.
• Coexistence of adenoma with carcinoma is not
uncommon.
Fundic gland polyps
• are also known as fundic gland hyperplasia or glandular
cysts.
• They are recognized as the most frequent type of
gastric polyp, accounting for nearly half of all gastric
polyps
• They are located exclusively in the acid-producing
mucosa and thus are not found in the antrum.
• The polyp may regress and may have no malignant
potential.
• Gastric polyps occurring as part of the familial
adenomatous polyposis syndrome are usually fundic
gland polyps.