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Gastric carcinoma Lecture 9

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Gastric carcinomaLecture 9

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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%

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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.

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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.

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Gastric cancer is more common in lower socioeconomic groups and in individuals with

multifocal mucosal atrophy and intestinal metaplasia.

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• Although overall incidence of gastric adenocarcinoma is falling,

•cancer of the gastric cardia is

on the rise.

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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.

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•occurs primarily after age 50 years

• with a 2: 1 male predominance. • The incidence of intestinal –type carcinoma has

progressively diminished in the US.

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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.

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• The intestinal and diffuse forms of gastric carcinomas can be considered as

distinct entities, although their clinical outcome is similar.

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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.

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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.

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• 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.

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• 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

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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.

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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.

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Morphology cont.

• Though less frequent, an ulcerative lesion on the

greater curvature is more likely to be

malignant than benign.

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Morphology cont.

• GC is classified on the basis of

• depth of invasion,

• Macroscopic growth pattern, and • Histologic subtype.

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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.

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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.

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Morphology cont.

Gastric mucosal dysplasia is

the presumed precursor lesion of

early gastric cancer,

which then in turn progresses to advanced lesions.

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•Part II

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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.

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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.

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Classification on the basis of histology

intestinal & diffuse.

Morphology cont.

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Morphology cont.

The intestinal variant is composed of

malignant cells forming neoplastic

intestinal glands resembling

those of colonic adenocarcinoma.

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• Gastric tumors with an intestinal morphology tend to form

bulky tumors

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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.

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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.

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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

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• 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.

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For obscure reasons, In advanced cases gastric carcinoma

the earliest lymph node metastasis may sometimes involve a

Supraclavicular lymph node (Virchow node).

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Rudolf Karl Virchow

Virchow - German pathologist (1821-1902)

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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.

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• Another somewhat unusual mode of intraperitoneal spread in females is to both the ovaries, giving rise to the so called

Krukenburg tumor.

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Local invasion into

the duodenum, pancreas, Retroperitoneum

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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

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Clinical featuresEarly stage:• Indigestion and stomach discomfort• A bloated feeling after eating• Mild nausea• Loss of appetite• Heartburn

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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).

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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

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TreatmentChemotherapy or radiation therapy and

palliative care. However, when possible, surgical resection remains the preferred

treatment for gastric adenocarcinoma.

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Prognosis• After surgical resection, the 5-year survival

rate of early gastric cancer

can exceed 90%, even if lymph node metastases are present.

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Prognosis cont.

• In contrast, the 5-year survival rate for

advanced gastric cancer remains

below 20%.

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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.

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