CARCINOMA OF THE GALLBLADDER
CARCINOMA OF THE GALLBLADDER
INTRO
• Most common malignancy of the extrahepatic biliary tract• Slightly more common in women • Occurs most frequently in the seventh
decade of life• Mean 5-year survival rate has remained for
many years at about 5% to 12% despite surgical intervention
• The most common sites of involvement are the fundus and the neck; about 20% involve the lateral walls.
ETIOLOGY
• The most important risk factor associated with gallbladder carcinoma is gallstones (cholelithiasis), which are present in 95% of cases• However, it should be noted that only 0.5%
of patients with gallstones develop gallbladder cancer after twenty or more years
• Carcinogenic derivatives of bile acids are believed to play a role.• Genetic factors • Previous surgery on the biliary tract • IBD
MORPHOLOGY
• Carcinomas of the gallbladder show two patterns of growth: infiltrating and exophytic
• The infiltrating pattern is more common and usually appears as a poorly defined area of diffuse thickening and induration of the gallbladder wall that may cover several square centimeters or may involve the entire gallbladder.
• Deep ulceration can cause direct penetration of the gallbladder wall or fistula formation to adjacent viscera into which the neoplasm has grown.
• These tumors are scirrhous and have a very firm consistency
• The exophytic pattern grows into the lumen as an irregular, cauliflower mass but at the same time invades the underlying wall.
• The luminal portion may be necrotic, hemorrhagic, and ulcerated
The opened gallbladder contains a large, exophytic tumor that virtually fills the lumen
HISTOLOGY
• Most carcinomas of the gallbladder are adenocarcinomas.
• Some of the carcinomas are papillary in architecture and are well to moderately differentiated; others are infiltrative and poorly differentiated to undifferentiated
• About 5% are squamous cell carcinomas or have adenosquamous differentiation
NORMAL ADENOCARCINOMA
Malignant glandular structures are present within a densely fibrotic gallbladder wall.
Papillary pattern
• By the time these neoplasms are discovered, most have invaded the liver centrifugally, and many have extended to the cystic duct and adjacent bile ducts and portal-hepatic lymph nodes.
• The peritoneum, gastrointestinal tract, and lungs are common sites of seeding.
GASTRIC ADENOCARCINOMA
INTRO
• Adenocarcinoma is the most common malignancy of the stomach, comprising over 90% of all gastric cancers
• Early symptoms resemble those of chronic gastritis. As a result, these tumors are often discovered at advanced stages,
EPIDEMIOLOGY
• Gastric cancer incidence varies markedly with geography
• The cause of the overall reduction in gastric cancer is unknown.
• One possible explanation is the decreased consumption of dietary carcinogens, such as N-nitroso compounds and benzopyrene, because of reduced use of salt and smoking for food preservation and the widespread availability of food refrigeration.
• Conversely, intake of green, leafy vegetables and citrus fruits, which contain antioxidants such as vitamin C, vitamin E, and beta-carotene, and is correlated with reduced risk of gastric cancers, may have increased as a result of improved food transportation networks.
• Gastric cancer is more common in lower socioeconomic groups and in individuals with multifocal mucosal atrophy and intestinal metaplasia.
• PUD does not impart an increased risk of gastric cancer, but patients who have had partial gastrectomies for PUD have a slightly higher risk of developing cancer in the residual gastric stump as a result of hypochlorhydria, bile reflux, and chronic gastritis.
• Although overall incidence of gastric adenocarcinoma is falling, cancer of the gastric cardia is on the rise.
• This is probably related to Barrett esophagus and may reflect the increasing incidence of chronic GERD and obesity.
ETIOPATHOGENESIS
• Helicobacter Pylori Infection: • Chronic H. pylori infection is the most important cause of
distal gastric adenocarcinoma • It commonly generates chronic gastritis, and over
several decades may induce mucosal atrophy, which in some patients precedes the development of cancer .
• Bacterial virulence factors, such as CagA and Vac A (vacuolating enzyme), play an important role in the severity of gastritis and intestinal metaplasia
• Dietary and Lifestyle Factors: • Smoking and dietary habits (high intake of salt-preserved
and/or smoked foods) also play a role in increasing cancer risk, either individually or by compounding the role of H. pylori infection
• Genetic Susceptibility • Some individuals are at increased risk of developing
gastric cancer, as well as other malignancies, because of dominantly inherited cancer predisposition syndromes, such as FAP, Lynch syndrome, and Li-Fraumeni syndrome . Patients with Peutz-Jeghers are also at risk for developing gastric cancers
• Hereditary Diffuse Gastric Cancer (HDGC):• Familial diffuse gastric cancer with autosomal dominant
inheritance, caused by germline mutation of E-cadherin(CDH1), is a recently reported syndrome
• Precursor Lesions• Whether in H. pylori-associated chronic gastritis or
autoimmune gastritis, atrophy followed by intestinal metaplasia develops over time, beginning a sequence of events that may culminate in neoplasia, particularly adenocarcinoma of tubular type.
• Gastric Polyps: Various polypoid lesions have the potential to develop into adenocarcinoma
• Adenomatous Polyps: The risk of malignant transformation is related to size (>2 cm) and the presence of high-grade intraepithelial neoplasia/dysplasia
• Non-neoplastic Polyps: Hyperplastic polyps and rare syndromic examples, as well as hamartomatous polyps that generally occur as part of hereditary polyposis syndromes (Peutz-Jeghers polyp, juvenile polyp, Cronkhite-Canada syndrome-associated polyp), also may undergo malignant transformation
MORPHOLOGY
• Most gastric adenocarcinomas involve the gastric antrum; the lesser curvature is involved more often than the greater curvature
• Gastric tumors with an intestinal morphology tend to form bulky tumors composed of glandular structures , while cancers with a diffuse infiltrative growth pattern are more often composed of signet-ring cells
Gastric adenocarcinoma. Intestinal-type adenocarcinoma consisting of an elevated mass with heaped-up borders and central ulceration.
NORMAL HISTOLOGY
Gastric adenocarcinoma. Intestinal-type adenocarcinoma composed of columnar, gland-forming cells infiltrating through desmoplastic stroma.
• When there are large areas of infitration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastica
• Breast and lung cancers that metastasize to the stomach may also create a linitis plastica–like appearance.
Linitis plastica. The gastric wall is markedly thickened, and rugal folds are partially lost.
Signet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent-shaped nuclei.
CLINICAL FEATURES
• Intestinal-type gastric cancer predominates in high-risk areas and develops from precursor lesions including flat dysplasia and adenomas. The mean age of presentation is 55 years, and the male-to-female ratio is 2 : 1.
• In contrast, 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.
• The depth of invasion and the extent of nodal and distant metastasis at the time of diagnosis remain the most powerful prognostic indicators for gastric cancer
• In advanced cases gastric carcinoma may first be detected as metastases to the supraclavicular sentinel lymph node, also called Virchow's node.
• 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.
• Local invasion into the duodenum, pancreas, and retroperitoneum is also characteristic. In such cases efforts are usually focused on chemotherapy or radiation therapy and palliative care
• Surgical resection remains the preferred treatment for gastric adenocarcinoma.
• After surgical resection, the 5-year survival rate of early gastric cancer can exceed 90%, even if lymph node metastases are present. In contrast, the 5-year survival rate for advanced gastric cancer remains below 20%
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