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 tumorthat 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
Malignant glandular structures Papillary patternare present within a denselyfibrotic gallbladder wall.
• 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.
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 adenocarcinomaconsisting of an elevated mass with heaped-up borders andcentral ulceration.
• 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, andrugal folds are partially lost.
Signet-ring cells can be recognized by their largecytoplasmic 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 Virchows 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%