GASTRIC ADENOCARCINOMAAdenocarcinoma is the most common malignancy of the stomach, comprising over90% -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 theincidence is up to 20-fold higher than in North America, northern Europe,Africa, and Southeast Asia.
In the United States, gastric cancer rates dropped byover 85% during the twentieth century. Similar declines havebeen reported in many other Western countries, suggesting thatenvironmental and dietaryfactors are responsible.One possible explanation isthe decreased consumption of dietary carcinogens.Intake of green, leafy vegetables and citrus fruits.
Gastric cancer is more common inlower socioeconomic groups and in individuals withmultifocal mucosal atrophy and intestinal metaplasia.
• Although overall incidence of gastricadenocarcinoma is falling,•cancer of thegastric cardiais 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 chronicgastritis.• 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 hasprogressively diminished in the US.
II.The diffuse variantarise de novo from native gastric mucous cells, isnot associated with chronic gastritis,poorly differentiated.occurs at an earlier agewith female predominance.The incidence of diffuse GA has not changed significantly in the past 60years and now constitutes approximately half of gastric carcinomas in theUS.
• The intestinal and diffuse forms of gastric carcinomas can be considered asdistinct entities, although their clinical outcome issimilar.
The incidence of diffuse gastric cancer is relatively uniformacross countries, there are no identified precursor lesions, andthe disease occurs at similar frequencies in males andfemales.
Risk Factors• Gender -- men have more than double the risk ofgetting stomach cancer than women.• Race -- being African-American or Asian mayincrease your risk.• Genetics -- genetic abnormalities and someinherited cancer syndromes may increase your risk• Geography -- stomach cancer is more common inJapan, the former Soviet Union, and parts of CentralAmerica and South America.• Blood type -- individuals with blood group A may beat increased risk.
• Advanced age -- stomach cancer occurs more oftenaround ages 70 and 74 in men and women,respectively.• Family history of gastric cancer can double or triple therisk of stomach cancer.• Lifestyle factors such as smoking, drinking alcohol, andeating a diet low in fruits and vegetables or high insalted, smoked, or nitrate-preserved foods mayincrease 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, nickelrefining, and rubber and timber processing andasbestos exposure.
• Diffuse Carcinoma (Risk factors)• Risk factors undefined, except for a rare inherited mutation ofE-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 andfundus.• The lesser curvature is involved in about 40% and thegreater curvature in 12%.• Thus, a favored location isthe lesser curvature of the antropyloric region.
Morphology cont.• Though less frequent, an ulcerative lesion on thegreater curvature is more likely to bemalignant 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 themucosa 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 extendedbelow the submucosa into the muscular walland has perhaps spread more widely.Morphologycont.
Morphology cont.Gastric mucosal dysplasia isthe presumed precursor lesion ofearly gastric cancer,which then in turn progresses to advanced lesions.
Classification on the basis of macroscopic growth patterns• The three macroscopic growth patterns of gastriccarcinoma which may be evident at both the early and advanced stages, are1.Exophyticwith protrusion of a tumor mass into the lumen;2.Flat or depressed, in which there is no obvious tumor mass within the mucosa; and3.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 anadenoma.• Flat or depressed malignancy presents only as regional effacementof the normal surface mucosal pattern.• Excavated cancers may mimic, in size andappearance, chronic peptic ulcers,although more advanced cases show heaped-upmargins.
Classification on the basis of histologyintestinal& diffuse.Morphology cont.
Morphology cont.The intestinal variant is composed ofmalignant cells forming neoplasticintestinal glands resemblingthose of colonic adenocarcinoma.
• Gastric tumors with an intestinalmorphology tend to formbulky tumors
Morphology cont.• The diffuse variant is composed ofgastric –type mucous cells thatgenerally do not form glands but ratherpermeate the mucosa and wall as scatteredindividual• signet-ring cells or• small clusters in an infiltrative growthpattern.
Morphology cont.A mass may be difficult to appreciate in diffuse gastric cancer, butthese infiltrative tumors often evoke aDesmoplasticreaction that stiffensthe gastric wall andmay provide a valuable diagnostic clue.
Morphology cont.The rigid and thickened stomachis termed a leather bottle stomach, or linitis plasticadue to desmoplastic reaction ( in diffuse variant).Brintons disease
• Whatever the histologic variant, all gastric carcinomas eventually penetrate the wall to involve theserosa,spread to regional and more distantlymph nodes, andmetastasize widely.
For obscure reasons, In advanced cases gastric carcinomathe earliest lymph node metastasismay sometimes involve aSupraclavicularlymph node(Virchow node).
Rudolf Karl VirchowVirchow- German pathologist(1821-1902)
Gastric tumors can also metastasize to the periumbilical regionto form a subcutaneous nodule, termed aSister Mary Joseph nodule,after the nurse who first noted this lesion as a marker of metastatic carcinoma.
• Another somewhat unusual mode ofintraperitoneal spread in females is to boththe ovaries, giving rise to the so calledKrukenburg tumor.
Local invasion intothe duodenum,pancreas,Retroperitoneum
Gastric adenocarcinoma. A, Intestinal-type adenocarcinoma consisting of an elevatedmass with heaped-up borders and central ulceration. B, Linitis plastica. The gastricwall 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 theabdomen.• Blood in the stool (which appears as black, tarrystools).• 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).
TreatmentChemotherapy orradiation therapy andpalliative care.However, when possible, surgical resection remains the preferredtreatment for gastric adenocarcinoma.
Prognosis• After surgical resection, the 5-year survivalrate of early gastric cancercan exceed 90%,even if lymph node metastases are present.
Prognosis cont.• In contrast, the 5-year survival rate foradvanced gastric cancerremainsbelow 20%.
PreventionGeneral MeasuresScreening(Mass endoscopic screening programs)The only hope for cure is early detection andsurgical removal, because the most importantprognostic indicator is stage of the tumor at the time ofresection.