Deases of the stomach

1
Peptic ulcer disease

2
 Definition

• A peptic ulcer is a break in the gastric or

duodenal mucosa that penetrates down to the
muscularis mucosae

3
 Epidemiology

• The incidence : 0.1% to 0.3% per year.

• become more common with increasing age

• more common in men than in women.

• Persons infected with Helicobacter pylori have

a tenfold increase in incidence.

• the prevalence has been decreasing during

the past several decades

5
 PATHOPHYSIOLOGY

• Peptic ulcers are the result of an imbalance

between mucosal insults and mucosal defense
mechanisms.

• protective mechanisms :

• surface mucus and bicarbonate layer,

• the epithelial barrier,

• tight intercellular junctions,

• mucosal blood flow-

• epithelial renewal
6
8
 PATHOPHYSIOLOGY
• The most common insults

• H. pylori infection

• Nonsteroidal antiiflammatory drugs (NSAIDs).

• Uncommon causes

• gastric acid hypersecretion (as in Zollinger-

Ellison syndrome),

• antral G-cell hyperplasia,

• mastocytosis.

• Viral infections with herpes simplex virus and

cytomegalovirus, inflammatory disorders such as
Crohn’s disease or sarcoidosis, and radiation injury
9
 1.Hp- epidemiology

• H. pylori infection is the major cause of PUD

• high prevalence regions, ( Southern Europe

and Japan ) : prevalence rate >90%,

• low prevalence regions ( Northern Europe and

the United States ) : 50% to 75%.

• The specific mode of transmission : person to

person. (oral-oral or fecal-oral routes. )

1
0
• H. pylori is a gram-negative
helical-shaped bacterium

• Colonize only gastric

epithelium.

• When they are found elsewhere

in the gastrointestinal tract (eg,
the gastroesophageal junction
or duodenum), they are
associated with metaplastic
gastric epithelium.

• To survive the hostile

environment of the stomach, H.
pylori produce urease that
generates ammonia.
- The critical role of H. pylori
in the development of PUD
is clear.
- What is not clear is why so
few patients with H. pylori
infection develop clinical
ulcerations.
Important factors :
• Host immune responses,
• Genetic predisposition,
• Bacterial virulence factors
 HP
antrum

loss of D cells that

release
somatostatin

release of gastrin
by antral G cells.

increased gastric acid

secretion
ulcer.
1
4
 2. Nonsteroidal Antiinflammatory
Drugs

• In the United States, up to 17 million people

take NSAIDs daily.

• Of these, 200,000 will have serious side effects

(including gastrointestinal tract bleeding) and
approximately 6,000 will die.

• Up to 3% of all NSAID users will develop serious

gastrointestinal complications (symptomatic
PUD, bleeding, or perforation), and 20% will
develop asymptomatic PUD or gastropathy
within the first year of use.
1
5
 Nonsteroidal Antiinflammatory Drugs

• NSAIDs disrupt the gastrointestinal tract

mucosal defense mechanisms by :

• topical : by direct injury to the gastric

epithelium.

• systemic effects

1
6
NSAI
D • disrupts mucosal blood
flow
inhibition of
prostaglandi • alters mucus secretion
mucosal
ns
• inhibits bicarbonate injury
secretion

••
break the tight
intercellular junctions release cytokines
increase the
inflammatory
• trapp of neutrophils
within the capillaries.

1
7
 Cyclooxygenase-2 Inhibitors

• = selective NSAIDs with less risk of

gastrointestinal complications than
nonselective NSAIDs.

• many drugs from this class have been

removed from the US market because of an
apparent increase in risk of stroke and
cardiovascular disease.

1
9
 Nonsteroidal Antiinflammatory Drugs
• The American College of Gastroenterology has
listed the five most important characteristics
that place patients at risk for NSAID-related
gastrointestinal complications:

• previous history of a gastrointestinal event

(ulcer or hemorrhage),

• age older than 60 years

• high dosage of NSAIDs

• concurrent use of glucocorticoids, and

concurrent use of anticoagulants.
2
0
 3.Gastric Acid

• The long-held dictum “no acid, no ulcer” still

applies.

• Once there is a mucosal break is maintained

and propagated by the presence of gastric
acid.

2
1
2
2
 Clinical features
• clinical features of PUD range from :

• silent ulceration to dyspepsia and epigastric

pain.

• The classic clinical feature of PUD :

• pain that occurs 2 to 3 hours after a meal

• improves with food or antacids,

• awakens the patient several hours after the

patient falls asleep.

2
3
 Diagnosis

• upper gastrointestinal tract radiographic

study

• esophagogastroduodenoscopy (EGD).

• The findings of these two tests correlate in

about 80% to 100% of cases.
2
4
2
5
2
6
Diagnostic Tests for Helicobacter
pylori

2
7
 Noninvasive Tests
• Serology

• Indication : For patients who have PUD and

have not been treated previously for H. pylori
infection,

• This test is inexpensive and noninvasive,

and it is as sensitive and specific as biopsy for
the initial diagnosis of H. pylori infection.

• limitations:

• it only provides evidence of the patient being

infected at some point with H. pylori but does
not provide information about current
infection. 2
8
 Stool Antigen Diagnosis of Helicobacter pylori
Infection

• Is highly accurate.

• It is noninvasive, simple, and costeffective.

• Its advantage over serologic testing :

• evaluates active infection ( it can be used

both as an initial test and as a test to evaluate
for eradication).

2
9
 Urease Breath Test

• This test is accurate, but it also depends on

bacterial load, making it prone to false-
negative results in patients who recently
received antibiotic or proton pump inhibitors.

• = the test used to confirm the eradication of

infection, but it should be performed 4 to 6
weeks after therapy has been completed.

3
0
 Invasive Tests - Histology

• “gold standard” for the diagnosis of active H.

pylori infection.

• It has been recommended that two biopsy

specimens be taken from the gastric antrum,
two from the gastric fundus, and one from the
incisura to yield the greatest sensitivity.

3
1
 Treatment

• The treatment of PUD has changed

remarkably since H. pylori infection has been
identified and associated with PUD.

• The recurrence rate of PUD has decreased

from up to 95% at 1 year to less than 10%
after H. pylori eradication.

• We have to consider H. pylori infection as a

potential cause of ulcer disease in all patients.

3
2
 Treatment of Helicobacter pylori Infection

• A 10- to 14-day course of therapy with

bismuth and antibiotics or with a proton
pump inhibitor and antibiotics is as effective
for inducing ulcer healing as a 4-week course
of proton pump inhibitor therapy.

• Combination therapy enhances the cure of H.

pylori infection, shortens the treatment
period, and has a 90% cure rate at 1 week.

3
3
The different treatment regimens for H. pylori
infection

3
4
 Antisecretory Treatment
Proton Pump Inhibitors

• Once-daily doses of omeprazole, from 20 to 40

mg, result in duodenal ulcer healing in 63% to
93% of patients at 2 weeks and in 80% to
100% at 4 weeks.

• Proton pump inhibitors are the most powerful

drugs available to suppress gastric acid
secretion.

3
5
 Antacids

• Antacids that contain aluminum and

magnesium hydroxide

• =>heal ulcers by binding bile and inhibiting

pepsin.

• =>promote angiogenesis in injured mucosa.

• =>30-mL doses daily are needed to heal

• adverse effects : diarrhea (magnesium-

containing agents), constipation (aluminum-
containing agents), and sodium overload.
3
6
 Sucralfate

• Sucralfate = sulfated polysaccharide that is

compounded with aluminum hydroxide.

• prevents acute ulceration and heals chronic

ulcers without affecting the secretion of
gastric acid

• promotes angiogenesis and the formation of

granulation tissue.

3
7
 Misoprostol
• Misoprostol is a prostaglandin E1 analogue that exerts
a mucosal protective effect by stimulating the
secretion of mucus and bicarbonate and by enhancing
mucosal blood flow.

• doses : 400 to 800 mg daily, enhances duodenal ulcer

healing compared with

• The primary role of misoprostol = the prevention of

NSAID-induced gastroduodenal injury.

• Side effects : uterotropic , bleeding, cramps, and

spontaneous abortion in pregnant women.

• => limited widespread use of misoprostol for both the

treatment of PUD and the prevention of NSAID-induced
ulceration.
3
8
 H2-receptor antagonists

• 1970

• four H2-receptor antagonists (cimetidine,

famotidine, nizatidine, and ranitidine)

• they are overall one of the safest classes of

drugs available. Single-nocturnal dosing is at
least

3
9
 Lifestyle Modifications

• Dietary change is no longer advised.

• The only general measures recommended

• discontinue cigarette smoking

• avoid NSAIDs.

4
0
 FOLLOW-UP AND MAINTENANCE THERAPY
• Duodenal Ulcers : Patients with uncomplicated
duodenal ulcers without evidence of H. pylori infection
who have received treatment do not require further
endoscopy or radiography to ensure healing unless
they have recurrent or persistent symptoms.

• Gastric Ulcers : Repeat endoscopy with biopsy has

been advocated to confirm gastric ulcer healing to
ensure that the ulcer is benign.

• If the initial biopsy findings are negative, the yield of

follow-up studies is low.

• An adequate examination and biopsy require at least

four biopsy specimens from the ulcer margin and one
from the base, if the ulcer is not too deep and it
seems safe to do .
4
1
Gastritis

4
7
 Definitions

GASTRITIS
CLINICAL = =
ENDO
DYSPEPSIA
+ HISTO
• The term gastritis has been used to describe
endoscopic findings of the gastric mucosa (eg,
erythema, nodularity, and erosions)

• gastritis refers to the histologic finding of

gastric mucosal injury with inflammation.

• Gastropathy is the more appropriate term for

epithelial damage without associated
inflammation

4
8
 classification

• Most classification systems distinguish :

• acute, short-term gastritis : neutrophilic

infiltration

• chronic, long-term disease :

mononuclear cell infiltration.
 Acute gastritis
• The hallmark of acute gastritis = development of
hemorrhagic or erosive lesions soon after :

• exposure of the gastric mucosa to various

toxic substances

• immediately following a significant reduction

in mucosal blood flow.

• The most common substances associated with

acute gastritis are nonsteroidal antiinflammatory
drugs (NSAIDs), alcohol, and bile acids.

• decreased mucosal blood flow : trauma, burns,

hypothermia, , radiation and systemic
chemotherapy.
5
0
 Acute gastritis-treatment

• The most important intervention for acute

gastritis is the withdrawal of the offending
agent or treatment of the underlying condition
(eg, hypotension).

• The mainstay of treatment is the use of

aggressive acid suppression, such as a proton
pump inhibitor, to limit injury from gastric acid
in the setting of a compromised gastric
mucosa.

5
2
 CHRONIC GASTRITIS

Their importance relates to the fact that these gastritis are

risk factors for other conditions :
• PUD,
• gastric hyperplastic polyps,
• benign and malignant gastric tumors.
5
4
Three types of chronic gastritis are recognized :
 Histopathology

• at least five biopsy specimens obtained from

the stomach: two from the gastric antrum, one
from the incisura, and two from the body or
fundus

5
6
HP GASTRITIS/INFECTION
 RESCUE TR. refere to :
- subjects who have failed two or more
treatments
- patients who have failed initial therapy or
have an infection recurrence
 Chronic Atrophic Gastritis

• = chronic gastritis : loss of glands, mucosal

thinning, and metaplastic changes of the
epithelial cells.

• Atrophic gastritis :

• autoimmune, or type A

• functional or endocrine changes in the

antrum and body (type B).

6
5
 Autoimmune Atrophic Gastritis
• = severe diffuse atrophy +chronic
inflammation + epithelial metaplasia.

• It is the result of an immune response directed

against parietal cells and intrinsic factor.

• Asociated with increase in serum antibodies

to parietal cells and intrinsic factor.

• Other conditions :autoimmune

endocrinopathies (eg, Hashimoto’s thyroiditis,
thyrotoxicosis, myxedema, Addison’s disease,
and diabetes mellitus) and collagen vascular
disease (eg, Sjögren’s syndrome).
6
6
 Autoimmune Atrophic Gastritis
• clinical manifestations : achlorhydria,
hypergastrinemia, and anemia (which can be
due to iron deficiency or malabsorption of
vitamin B12 or both).

• increased risk of

• hyperplastic and adenomatous polyps,

• carcinoid tumors,

• gastric lymphoma,

• gastric adenocarcinoma.
6
7
 CMV gastritis
• Cytomegalovirus (CMV) is the most common
virus associated with gastritis.

• CMV can infect any cell within the

gastrointestinal tract, including the stomach.

• causes ulceration, but the endoscopic findings

can be vague.

• Biopsy specimens show mucosal

inflammation, vascular endothelial
involvement, and even tissue necrosis.

• diagnosed in the presence of

immunodeficiency.
6
9
 Special Forms of Gastritis
• Lymphocytic Gastritis

• is often asymptomatic

• Diagnostic : biopsy from normal, or only

slightly abnormal, appearing gastric mucosa

• The essential diagnostic feature is infiltration

of the surface epithelium with lymphocytes.

• is frequently encountered in patients with H.

pylori and celiac disease.

7
0
• Mycobacterium :in patients with disseminated
tuberculosis or systemic Mycobacterium

• Histology : necrotizing granulomas

• Granulomatous Gastritis :

• infectious and noninfectious diseases

can cause granulomatous

• infectious cause (eg, tuberculosis,

histoplasmosis, or syphilis)

• noninfectious conditions such as

Crohn’s disease, sarcoidosis, Wegener’s
granulomatosis or, rarely, gastric neoplasm.
7
1
 Eosinophilic Gastritis
• Eosinophilic gastritis is due to eosinophilic infiltration
that may involve the full thickness of the stomach.

• the gastric antrum is involved more often than the

body or fundus.

• has been associated with connective tissue disorders

such as scleroderma , parasitic larvae, (anisakiasis.)

• most cases of eosinophilic gastritis are idiopathic.

• Peripheral blood eosinophilia is found in up to 75% of

patients.

• The disease typically responds to systemic

corticosteroid therapy.
7
2
 GASTROPATHYS
• Vascular Gastropathies

• are abnormalities in the gastric tissue that

involve the mucosal vessels, with little or no
inflammation.

• most important vascular gastropathies

are :

• gastric antral vascular ectasia

(GAVE), or watermelon stomach

• portal hypertensive
7
gastropathy.
3
 Portal Hypertensive Gastropathy

• is associated exclusively with portal hypertension.

• is graded endoscopically as mild or severe. Severe

portal hypertensive gastropathy has active oozing or
hemorrhage.

• iron deficiency anemia (blood transfusion.)

• no effective endoscopic treatment. ( deep submucosal

vessels are involved )

• Treatment decreasing portal hypertension

:nonselective β-blockers, portal decompression (such
as transjugular intrahepatic portosystemic shunt), or
liver transplantation.
7
4
 Ménétrier’s Disease
Hipertrofic gastropaty
• nonspecific clinical features : abdominal pain,
weight loss, nausea, diarrhea, or proteinlosing
enteropathy.

• The diagnosis requires a fullthickness gastric

biopsy specimen or biopsy via endoscopic snare
of an enlarged fold.

• Histologic : extreme foveolar hyperplasia with

glandular atrophy.

• There is no proven treatment for Ménétrier’s

disease.
7
5
76
 GASTRIC NEOPLASMS AND
GASTROENTEROPANCREATIC
NEUROENDOCRINE TUMORS

7
7
• adenocarcinoma is the most common ( 95% )
of all gastric neoplasms.

• Less common :

• gastric lymphomas,

• gastrointestinal stromal tumors,

• neuroendocrine tumors

• metastatic disease involving the stomach

7
8
 ADENOCARCINOMA

• gastric adenocarcinoma = second most

common cancer worldwide

• 870,000 new cases/ year

• 650,000 deaths per year.

• Gastric cancer mortality rates have remained

relatively unchanged over the past 30 years,

7
9
 Epidemiology
• 60 % of gastric cancers occur in the developing
world.

• The highest incidence rates :Eastern Asia, South

America, and Eastern Europe.

• The lowest incidence rates are primarily in the

industrialized nations: North America, Northern
Europe, and Southeastern

• more common in men than in women

• The worldwide incidence of gastric cancer has

decreased over the past 2 decades (identification
and treatment of H. pylori infection and changes
in diet trends)
8
0
 Pathogenesis
• multiple causative factors :

• diet, exogenous substances,

• infectious agents,

• genetic factors.

• patients with gastric surgery are at higher risk for

the development of gastric cancer. (15 to 20
years after the operation)

• Billroth II surgery carries a higher risk than the

Billroth I surgery, ( Billroth II surgery increases the
reflux of bile and pancreatic juices)
8
2
 Risk Factors Diet
• Epidemiologic studies have documented an association
between diet and gastric cancer.

• The most consistent association is the ingestion of nitroso

compounds.

• Diets high in salt have also been linked with an increased

incidence of gastric cancer.

• Diets low in uncooked fruits (particularly citrus fruits) and

vegetables and high in processed meat, fried food, and
alcohol are associated with an increased risk of gastric
cancer.

• The protective effect provided by fruits and vegetables is

thought to be due to their vitamin C content, which may
decrease the formation of nitroso compounds inside the
stomach.
8
4
 Infections
• The two infections that have been associated with
an increased risk of the development of gastric
cancer are Epstein-Barr virus infection and
Helicobacter pylori infection.

• Epstein-Barr virus infection : 5% to 10% of gastric

cancers are associated with EB

• H. pylori = the most important risk factor for the

development of gastric cancer.

• H. pylori was the first bacteria linked to a human

cancer.

• H. pylori has been classified as a definite

carcinogen by the World Health Organization.
8
5
 Genetics
• First-degree relatives of patients with gastric
cancer have at least a twofold greater incidence
of this cancer than the general population.

• Gastric cancer occasionally develops in families

with germline mutations in the p53 gene (Li-
Fraumeni syndrome) and BRCA2.

• certain cancer syndromes have been associated

with gastric cancer : familial adenomatous
polyposis, hereditary nonpolyposis colorectal
cancer, and Peutz-Jeghers syndrome.

• Blood group A appears to confer an increased

risk of gastric cancer.
8
6
 Gastric disorders

• Pernicious anemia is an autoimmune-type

atrophic gastritis.

• Extended atrophic gastritis + IM ( displasia )

• Gastric polyps (Adenomatous polyps )

=>polipectomy

• Hypertrophic gastropathy (Ménétrier disease)

8
8
PATHOGENESIS
 Clinical Features
• are vague (epigastric pain, early satiety,
abdominal bloating, or meal-induced
dyspepsia )

• Weight loss, nausea, and anorexia are

common

• Distal antrum or pylorus : vomiting due to

gastric outlet obstruction.

• Occult or overt bleeding may occur in early- or

late-stage cancers.

• Dysphagia : cardia or gastroesophageal

junction.. 9
0
9
1
92
93
94
95
96
97
 Spreds :
• 1. Direct extension through the stomach wall to
perigastric tissue, and it invades : pancreas, colon,
spleen, kidney, or liver.

• 2. Lymphatic metastases occur early, and local and

regional nodes are the first to be involved.

• supraclavicular region (Virchow’s node),

• periumbilical area (Sister Mary Joseph’s nodule),

• left axilla (Irish node)

• peritoneal carcinomatosis

• 3. hematogenous spread : liver , lungs, bones, and

brain.
9
8
 Tumor Features

• 1. Location

• Proximal lesions ( cronic reflux ) are

more aggressive and have a worse prognosis
than distal cancers— ( related closely to
chronic H. pylori ) .

99
 Tumor Features

• 2. Infiltration

• The linitis plastica lesion occurs in up to 10%

of gastric adenocarcinomas.

• associated with locally advanced or metastatic

disease and portends a worse prognosis.

10
0
 Tumor Features
• 3. Histology

• two types: intestinal and diffuse.

• The intestinal type of adenocarcinoma has epithelial cells

that form discrete glands, microscopically resembling
colonic adenocarcinoma.

• It often arises within an area of intestinal metaplasia.

• better prognosis than the diffuse type.

• The diffuse type of gastric adenocarcinoma is

characterized by sheets of epithelial cells.. Mucus-
producing signet ring cells are often present .

• tends to be infiltrating, poorly differentiated, and

generally has a poor prognosis.
10
3
 Staging
• The most important aspect of staging is if the
cancer is resectable.

• Staging is both clinical and pathologic.

• Clinical stage - preoperatively,

• Pathologic staging is based on findings made

during surgical exploration and examination of
the pathology specimen.

• The TNM staging system of the American Joint

Committee on Cancer is used most frequently
10
4
TNM CLASSIFICATION
 Treatment
• Surgery =mainstay of treatment for gastric cancer.

• Complete surgical removal of a gastric tumor, with

resection of the adjacent lymph nodes, is the only
chance for cure.

• recurrence rate = 40% to 65% in patients who had

resection with curative intent.

• resistant to radiotherapy, which generally is

administered only to palliate symptoms and not to
improve survival.

• Chemotherapeutic regimens have shown only

modest results
10
7
108
 Prognosis
• Even with more advanced surgical techniques and
chemotherapeutic agents, the prognosis for gastric
adenocarcinoma remains grim for all but those who are
candidates for surgical resection.

• In general, 5-year survival rates can be approximated as

follows:

• stage IA, 80%-95%;

• IB, 60%-85%;

• II, 30%-50%;

• IIIA, 20%-40%; IIIB, 10%;

• IV, 7%.
11
1
GASTRIC LYMPHOMA

11
2
 Epidemiology

• Primary gastric lymphoma accounts for up to

10% of lymphomas and up to 5% of gastric
neoplasms.

• The stomach is the most common extranodal

site of lymphoma and accounts for
approximately 20% of all extranodal
lymphomas.

• peak incidence between the ages of 50 and 60

years

11
4
 Epidemiology

• the most frequent lymphomas are :

• low-grade extranodal marginal zone B-cell

lymphomas (ENMZLs) -formerly known as
mucosa-associated lymphoid tissue [MALT]
lymphomas

• diffuse large B-cell lymphomas (DLBCLs).

 Risk factors

• H. pylori-associated chronic gastritis

• autoimmune diseases

• immunodeficiency syndromes

• and long-term immunosuppressive therapy.

11
6
 Clinical features
• are nonspecific :

• abdominal discomfort,

• dyspepsia,

• gastric outlet complaints due to obstruction or

impairment of gastric motility,

• anorexia,

• weight loss,

• anemia due to blood loss from ulceration.

11
7
 Diagnostic Evaluation
• Endoscopically, has a broad range of appearances :

• large, firm rugal folds

• eroded nodules

• exophytic ulcerated masses.

• CT of the abdomen and chest => involvement of

regional lymph nodes, extension of the tumor into
surrounding structures, and distant

• EUS =>determining the extent of gastric wall

infiltration and can provide useful information for
treatment planning.
11
8
Extranodal Marginal Zone B-Cell
Lymphoma = MALT lymphoma

• associated with H. pylori infection (90% of

cases. )

• The best evidence supporting the role for H.

pylori in ENMZ = remission of the tumor after
eradication of H. pylori infection with antibiotic
therapy.

11
9
 Staging

• stage I disease is limited to the stomach

• stage II disease implies localized involvement

of the lymph nodes on the same side of the
diaphragm.

• stage III disease, both sides of the diaphragm

are involved.

• Stage IV disease is disseminated disease.

12
0
 Treatment MALT
• Only patients with localized, mucosal, or submucosal
flat lesions and without metastatic disease are
candidates for antimicrobial therapy alone.( eradication
of HP )

• eradication of the organism must be proven.

• Histologic regression requires several months

• standard therapies for lymphoma (systemic

chemotherapy, radiation, or surgery, )

• 90% survival rate at 5 years.

• Treatment failures or patients with recurrent or

extensive (stage III or IV) disease are treated with
multiagent chemotherapy
12
2
 TREATMENT DLBCL

• Stage 1- partial gastrectomy

• Stage II, III, or IV disease, the primary therapy

is sytemic chemotherapy.

• Radiotherapy generally is used to reduce the

size of large lesions and to control localized
disease.
 GASTROINTESTINAL STROMAL TUMORS

• tumors identical to those that arise in soft

tissues throughout the rest of the body
(lipomas, hemangiomas, schwannomas,
leiomyomas, and leiomyosarcomas)

• GISTs can occur anywhere in the

gastrointestinal tract but usually affect the
stomach and proximal small intestine.

12
4
 GASTROINTESTINAL STROMAL TUMORS

• Histology dg
• CD117 antigen allowed GISTs to be
differentiated from leiomyomas and other
similar tumors of the gastrointestinal tract

• It is known that the larger the tumor, the more

likely it will behave in a malignant fashion.

• When GISTs metastasize, it is usually to the

liver.

12
7
 Treatment

• Before the year 2000, resection was the only

therapy that could be offered to patients with
GISTs.

• Imatinib, a potent inhibitor of KIT signaling,

was first used.

• Complete resection is possible for most

localized GISTs, but only 50% of patients will
remain free of disease over 5 years.

12
8
 Prognosis
• Prognosis is influenced by :

• tumor site (small intestine worse than

stomach)

• tumor size (the larger, the worse the

prognosis),

• the ability to resect the tumor completely

• the response to imatinib in advanced disease.

12
9
 GASTROENTEROPANCREATIC NEUROENDOCRINE
TUMORS

• arise from neuroendocrine cells.

• include :

• carcinoid tumors

• pancreatic islet cell tumors (gastrinoma,

insulinoma, glucagonoma, VIPoma, and
somatostatinoma).

13
0
CARCINOID TUMORS AND CARCINOID SYNDROME

• are the most common GNETs,

• are slow growing

• can occur anywhere in the alimentary tract.

13
1
 Clinical and Tumor Features
• Symptoms : abdominal pain, intestinal
obstruction, nausea, weight loss, or intestinal
bleeding.

• Carcinoid tumors are rare, and those that

cause carcinoid syndrome are even rarer. ( 5%
)

• Carcinoid syndrome is due to peptides

released by the tumor into the systemic
circulation. (histamine, kallikrein,
prostaglandins, serotonin, and tachykinins. )

13
2
 carcinoid syndrome

• carcinoid syndrome : diarrhea and facial

flushing.

• The typical flush is red or violaceous and

appears on the face, neck, and upper chest+
hypotension + tachycardia.

• inciting factors : eating, alcohol ingestion, the

Valsalva maneuver, increased emotional
states, trauma, anesthesia.
134
135
 Stomach
• single or multiple,

• endoscopy : ordinary ulcer, polyp, or tumor

mass.

• Gastric carcinoid tumors occur more

frequently in patients who have a disease that
causes hypergastrinemia, such as pernicious
anemia and atrophic gastritis with
achlorhydria.

• They also appear to be more common in

patients with Zollinger-Ellison syndrome.

• divided into three separate types, each of

which has a different behavior
13
7
and prognosis.
 Type 1

• Up to 80% of all gastric carcinoids are type 1.

• associated with pernicious anemia or chronic

atrophic gastritis.

• Metastatic disease is rare and occurs in fewer

than 10% of tumors 2 cm or smaller but in as
many as 20% of larger

• often are considered a benign condition.

13
8
139
140
 Type 2
• Carcinoid tumors of the stomach due to hypergastrinemia from
gastrinomas

• are rare (<5% of gastric carcinoids)

• For types 1 and 2 gastric carcinoids smaller than 1 cm,

endoscopic resection, if possible, is the treatment of choice.

• endoscopic surveillance every 6 to 12 months has been

recommended,

• progression to malignant disease and death is unusual.

• For patients with multiple tumors or advanced disease that is

not appropriate for resection, antrectomy or medical therapy
aimed at reducing serum levels of gastrin has been advocated.
Antrectomy decreases hypergastrinemia by removing much of
the gastrin-producing cell mass in the stomach.
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 Type 3

• Type 3 gastric carcinoids are sporadic and do

not appear to be associated with
hypergastrinemia.

• are the most aggressive ( 65% of patients

have local or liver metastases at the time the
tumor is discovered)

• treated by partial or total gastrectomy with

local lymph node resection.

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 Diagnosis of Carcinoid Tumors
and Syndrome
• Most carcinoid tumors are found incidentally

• If symptoms of carcinoid syndrome are strongly

suspected, the best initial evaluation is with urinary
5-hydroxyindoleacetic acid. ( increased )

• Octreotide scintigraphy (Octreascan) identifies the

site of primary tumors and metastatic disease in
more than 80% of patients with carcinoid syndrome.

• Magnetic resonance imaging and selective

angiography are sensitive for detecting metastases
to the liver.
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GASTRINOMA
• Gastrinomas produce the classic triad of
symptoms called Zollinger-Ellison syndrome:

• peptic ulcer disease,

• gastric acid hypersecretion,

• gastrin-producing tumor.

• Gastrinomas are rare and occur in fewer than

1% of patients who have peptic ulcer disease.

• Gastrinomas are frequently associated with

MEN 1 syndrome.
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 Etiology and Pathogenesis
• One-half of gastrinomas occur in the duodenal
wall; the pancreas is the second most
common site.

• more than 90% of gastrinomas occur in an

anatomical area called the gastrinoma triangle

• difficult to differentiate benign tumors from

malignant

• Approximately two-thirds of gastrinomas are

malignant. (best indicator of malignancy is the
presence of metastases : regional lymph
nodes or the liver. ) 14
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 Clinical Features

• Peptic ulcer disease is the most common sign

of gastrinoma (90%).

• multiple duodenal ulcers (including postbulbar

ulcers) and esophagitis that is refractory to
medical treatment .

• 50% of the patients have diarrhea due to the

effect of acid hypersecretion on the small
bowel.

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• If a patient has a duodenal ulcer that is not
caused by either H. pylori infection or
nonsteroidal antiinflammatory drugs or if a
patient has duodenal ulcer disease and
diarrhea, the concurrent presence of
gastrinoma should be considered.

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 Diagnostic Tests

• the first screening test = serum level of

gastrin. (after proton pump inhibitor therapy
has been withheld for at least 7 days )

• A serum gastrin level of more than 1,000

pg/mL suggests the presence of gastrinoma.

• A level less than 1,000 pg/mL but more than

110 pg/mL may be consistent with several
conditions that cause hypergastrinemia.
(achlorhydria<= atrophic gastritis) .

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 Treatment

• Surgical resection = treatment of choice for

patients with resectable (ie, not metastatic or
locally advanced) disease.

• Patients with liver metastases or MEN 1

syndrome (with multifocal disease) = control
gastric acid hypersecretion =proton pump
inhibitors and octreotide.

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