Post on 28-Jan-2015
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Gastric carcinomaLecture 9
GASTRIC ADENOCARCINOMA
Adenocarcinoma is the most common malignancy of the stomach, comprising over
90% -95% of all gastric cancers.
• Lymphomas 4%• Carcinoid 3%• Stromal tumors 2%
Epidemiology & Classification
•
GC is the second leading cause of cancer-related deaths in the world after lung
cancer.
• In Japan, Chile, Costa Rica, and Eastern Europe the
incidence is up to 20-fold higher than in North America, northern Europe,
Africa, and Southeast Asia.
In the United States, gastric cancer rates dropped by over 85% during the twentieth century. Similar declines have
been reported in many other Western countries, suggesting that
environmental and dietary factors are responsible.
One possible explanation is
the decreased consumption of dietary carcinogens.
Intake of green, leafy vegetables and citrus fruits.
Gastric cancer is more common in lower socioeconomic groups and in individuals with
multifocal mucosal atrophy and intestinal metaplasia.
• Although overall incidence of gastric adenocarcinoma is falling,
•cancer of the gastric cardia is
on the rise.
Classification:GC show two morphologic types, called intestinal & diffuse.
I.The intestinal type • arise from gastric mucous cells that have undergone intestinal metaplasia in the setting of chronic gastritis.
• better differentiated • the more common type in high risk populations.
•occurs primarily after age 50 years
• with a 2: 1 male predominance. • The incidence of intestinal –type carcinoma has
progressively diminished in the US.
II.The diffuse variant arise de novo from native gastric mucous cells, is
not associated with chronic gastritis,
poorly differentiated. occurs at an earlier age with female predominance. The incidence of diffuse GA has not changed significantly in the past 60
years and now constitutes approximately half of gastric carcinomas in the US.
• The intestinal and diffuse forms of gastric carcinomas can be considered as
distinct entities, although their clinical outcome is similar.
The incidence of diffuse gastric cancer is relatively uniform across
countries, there are no identified precursor lesions, and the
disease occurs at similar frequencies in males and females.
Risk Factors• Gender -- men have more than double the risk of
getting stomach cancer than women.• Race -- being African-American or Asian may
increase your risk.• Genetics -- genetic abnormalities and some
inherited cancer syndromes may increase your risk• Geography -- stomach cancer is more common in
Japan, the former Soviet Union, and parts of Central America and South America.
• Blood type -- individuals with blood group A may be at increased risk.
• Advanced age -- stomach cancer occurs more often around ages 70 and 74 in men and women, respectively.
• Family history of gastric cancer can double or triple the risk of stomach cancer.
• Lifestyle factors such as smoking, drinking alcohol, and eating a diet low in fruits and vegetables or high in salted, smoked, or nitrate-preserved foods may increase your risk
• Helicobacter pylori• Certain health conditions including chronic gastritis,
pernicious anemia, gastric polyps, intestinal metaplasia, and prior stomach surgery.
• Work-related exposure due to coal mining, nickel refining, and rubber and timber processing and asbestos exposure.
• Diffuse Carcinoma (Risk factors)
• Risk factors undefined, except for a rare inherited mutation of
E-cadherin• Infection with H. pylori and chronic gastritis often absent
Pathogenesis• The mechanisms of neoplastic transformation are not entirely clear.
• Chronic inflammation induced by H. pylori
• may release reactive oxygen species,• which eventually cause DNA damage, • leading to an imbalance between cell proliferation and apoptosis, particularly in areas of tissue repair.
Morphology• The location of gastric carcinoma within the stomach is as follows:
• Pylorus and antrum, 50% to 60%;
• Cardia 25%; and
• the remainder (15-25%) in the body and fundus.
• The lesser curvature is involved in about 40% and the
greater curvature in 12%.• Thus, a favored location is
the lesser curvature of the antropyloric region.
Morphology cont.
• Though less frequent, an ulcerative lesion on the
greater curvature is more likely to be
malignant than benign.
Morphology cont.
• GC is classified on the basis of
• depth of invasion,
• Macroscopic growth pattern, and • Histologic subtype.
Classification on the basis of depth of Invasion• Early gastric carcinoma is defined as a lesion confined to the
mucosa and submucosa, regardless of the presence or absence of perigastric lymph node metastases.
Morphology cont.
Classification on the basis of depth of Invasion
• Advanced gastric carcinoma is a neoplasm that has extended
below the submucosa into the muscular wall and has perhaps spread more widely.
Morphology cont.
Morphology cont.
Gastric mucosal dysplasia is
the presumed precursor lesion of
early gastric cancer,
which then in turn progresses to advanced lesions.
•Part II
Classification on the basis of macroscopic growth patterns
• The three macroscopic growth patterns of gastric
carcinoma which may be evident at both the early and advanced stages, are
1.Exophytic with protrusion of a tumor mass into the lumen;
2.Flat or depressed, in which there is no obvious tumor mass within the mucosa; and
3.Excavated, whereby a shallow or deeply erosive crater is present in the wall of the stomach.
Morphology cont.
Morphology cont.
• Exophytic tumors may contain portions of an
adenoma. • Flat or depressed malignancy presents only as regional effacement
of the normal surface mucosal pattern.
• Excavated cancers may mimic, in size and
appearance, chronic peptic ulcers, although
more advanced cases show heaped-up margins.
Classification on the basis of histology
intestinal & diffuse.
Morphology cont.
Morphology cont.
The intestinal variant is composed of
malignant cells forming neoplastic
intestinal glands resembling
those of colonic adenocarcinoma.
• Gastric tumors with an intestinal morphology tend to form
bulky tumors
Morphology cont.
• The diffuse variant is composed of gastric –type mucous cells that generally do not form glands but rather permeate the mucosa and wall as scattered individual
• signet-ring cells or • small clusters in an infiltrative growth
pattern.
Morphology cont.A mass may be difficult to appreciate in diffuse gastric cancer, but
these infiltrative tumors often evoke a
Desmoplastic reaction that stiffens the gastric wall and
may provide a valuable diagnostic clue.
Morphology cont.
The rigid and thickened stomach is termed a leather bottle stomach, or linitis plastica due
to desmoplastic reaction ( in diffuse variant).
Brinton's disease
• Whatever the histologic variant, all gastric carcinomas eventually penetrate the wall to involve the
serosa, spread to regional and more distant
lymph nodes, and
metastasize widely.
For obscure reasons, In advanced cases gastric carcinoma
the earliest lymph node metastasis may sometimes involve a
Supraclavicular lymph node (Virchow node).
Rudolf Karl Virchow
Virchow - German pathologist (1821-1902)
Gastric tumors can also metastasize to the periumbilical region
to form a subcutaneous nodule, termed a
Sister Mary Joseph nodule, after the nurse who first noted this lesion as a marker of metastatic carcinoma.
• Another somewhat unusual mode of intraperitoneal spread in females is to both the ovaries, giving rise to the so called
Krukenburg tumor.
Local invasion into
the duodenum, pancreas, Retroperitoneum
Gastric adenocarcinoma. A, Intestinal-type adenocarcinoma consisting of an elevated mass with heaped-up borders and central ulceration. B, Linitis plastica. The
gastric wall is markedly thickened, and rugal folds are partially lost.
Diffuse type
Clinical featuresEarly stage:• Indigestion and stomach discomfort• A bloated feeling after eating• Mild nausea• Loss of appetite• Heartburn
Clinical featuresAdvanced stage:• Discomfort in the upper or middle part of the
abdomen.• Blood in the stool (which appears as black, tarry
stools).• Vomiting or vomiting blood.• Weight loss.• Pain or bloating in the stomach after eating.• Weakness or fatigue associated with mild anemia
(a deficiency in red blood cells).
Diagnosis• Signs& symptoms• Medical History & Physical exam• Upper endoscopy• Biopsy• Testing Biopsy• Imaging tests• Endoscopic Ultrasound• CT scan• MRI• PET• Chest X-ray• Laparoscopy• Lab tests
TreatmentChemotherapy or radiation therapy and
palliative care. However, when possible, surgical resection remains the preferred
treatment for gastric adenocarcinoma.
Prognosis• After surgical resection, the 5-year survival
rate of early gastric cancer
can exceed 90%, even if lymph node metastases are present.
Prognosis cont.
• In contrast, the 5-year survival rate for
advanced gastric cancer remains
below 20%.
PreventionGeneral Measures
Screening(Mass endoscopic screening programs)
The only hope for cure is early detection and surgical removal, because the most important prognostic indicator is stage of the tumor at the time of resection.