Gastric Carcinoma PDF

GASTRIC CARCINOMA DR. JIBRAN AHMED MJN MEDICAL COLLEGE AND HOSPITAL  Adenocarcinoma is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers. Most distal gastric adenocarcinomas occur in the gastric antrum; the lesser curvature is involved m...

GASTRIC CARCINOMA DR. JIBRAN AHMED MJN MEDICAL COLLEGE AND HOSPITAL  Adenocarcinoma is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers. Most distal gastric adenocarcinomas occur in the gastric antrum; the lesser curvature is involved more often than the greater curvature. Early symptoms of both types of gastric adenocarcinoma resemble those of chronic gastritis and peptic ulcer disease, including dyspepsia, dysphagia, and nausea. As a result, these tumors are often discovered at advanced stages, when symptoms such as weight loss, anorexia, early satiety (primarily in diffuse cancers), anemia, and hemorrhage appear. GENETICS PATHOGENESIS Familial gastric cancer – Is strongly associated with germline loss-of-function mutations in the tumor suppressor gene CDH1, which encodes the cell adhesion protein E-cadherin. Diffuse Gastric Carcinomas – Loss-of-function mutations in CDH1 are also present in about 50% of sporadic diffuse gastric tumors, while E-cadherin expression is drastically decreased in the remainder of diffuse tumors, often by hypermethylation and silencing of the CDH1 promoter. Thus, E-cadherin loss is a key step in the development of diffuse gastric cancer. Intestinal-type gastric cancers – Are strongly associated with mutations that result in increased signaling via the Wnt pathway. These include loss-of-function mutations in the adenomatous polyposis coli (APC) tumor suppressor gene and gain-of-function mutations in the gene encoding β-catenin. – Loss-of-function mutations or silencing include those involved in TGF-β signaling ; regulation of apoptosis (BAX), and cell cycle control (CDKN2A); – FAP patients with germline APC mutations have an increased risk of intestinal-type gastric cancer. In association with other familial Sx like FAP, HNPCC….. Blood group A(increases risk) Variants of proinflammatory genes such as IL-1β and IL-1 receptor, are associated with elevated risk of gastric cancer in those who have H. pylori gastritis. ENVIRONMENTAL FACTORS Gastric cancer is more common in lower socioeconomic groups and in individuals with multifocal mucosal atrophy and intestinal metaplasia H. Pylori Infection(More commonly associated with Intestinal type carcinoma) Peptic ulcer disease is associated with reduced risk of gastric cancer, but patients who have had partial gastrectomies for peptic ulcer disease have a slightly higher risk of developing cancer in the residual gastric stump. N-nitroso compounds and benzo[a]pyrene used as preservatives in food. Smoked and salted food. HOST FACTORS: CHRONIC GASTRITIS BARRETT’S ESOPHAGUS(CHRONIC GERD AND OBESITY)—INTESTINAL METAPLASIA—GASTRIC CARDIA ADENOCA; MENETRIER’S DISEASE GASTRIC ADENOMA INTESTINAL VS DIFFUSE TYPE  INTESTINAL TYPE DIFFUSE TYPE 1. GENETICS—LOF MUT IN APC/GOF IN B- 1. GENETICS—LOF CATENIN; LOF MUT IN TGF-B;BAX;CDKN2A; MUT/HYPERMETHYLATION/SILENCING OF FAP CDH-1(E-CADHERIN)GENE 2. GROSS—BULKY;EXOPHYTIC 2. GROSS—DIFFUSE INFILTRATIVE GROWTH MASS/ULCERATIVE INFILTRATIVE LESION PATTERN WITH MARKEDLY THICKENED WITH HEAPED UP BORDERS. GASTRIC WALLS AND PARTIAL LOSS OF RUGOSITY(LINITIS PLASTICA/LEATHER BOTTLE APPEARANCE); NO MASS 3. M/E—GLAND FORMATION IN A 3. M/E—DIFFUSE CANCERS PERMEATE THE INFILTRATIVE DESMOPLASTIC STROMA GASTRIC WALL AS SMALL CLUSTERS AND INDIVIDUAL DISCOHESIVE CELLS DUE TO THE ABSENCE OF E-CADHERIN. THESE CELLS DO NOT FORM GLANDS BUT INSTEAD HAVE LARGE MUCIN VACUOLES THAT EXPAND THE CYTOPLASM AND PUSH THE NUCLEUS TO THE PERIPHERY, CREATING A SIGNET-RING CELL MORPHOLOGY Release of extracellular mucin in either type of gastric cancer can result in formation of large mucin lakes. Gastric adenocarcinoma. Intestinal-type adenocarcinoma consisting of an elevated mass with heaped-up borders and central ulceration. Diffuse Infiltrative type (linitis plastica) gastric cancer. The gastric wall is markedly thickened, and rugal folds are partially lost, but there is no dominant mass. Gastric adenocarcinoma. (A) Intestinal-type adenocarcinoma composed of columnar, gland-forming cells infiltrating through Desmoplastic stroma. (B) In infiltrative tumors, signet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent- shaped, thin nuclei. Note the absence of gland formation. DEPTH OF INVASION 1. EARLY GASTRIC CARCINOMA(SUPERFICIAL SPREADING TYPE)—Tx involving mucosa and submucosa irrespective of L.N involvement. Has best prognosis. 2. ADVANCED GASTRIC CARCINOMA—Tx involves beyond submucosa into muscular wall The depth of invasion and the extent of nodal and distant metastases remain the most powerful prognostic indicators in gastric cancer. Local invasion into the duodenum, pancreas, and retroperitoneum is common. In such cases efforts are usually focused on chemotherapy or radiation therapy and palliative care. When possible, surgery remains the preferred treatment approach. With 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 less than 20%. Because of the advanced stage at which most gastric cancers are discovered, the overall 5-year survival is less than 30%.  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, and there are no identified precursor lesions. Prevalence is similar in males and females Notably, the remarkable decrease in gastric cancer incidence applies only to the intestinal type. As a result, the incidences of intestinal- and diffuse-type gastric cancers are now similar in many regions. Metastases are often present at diagnosis. Sites most commonly involved include supraclavicular sentinel lymph nodes (Virchow node), periumbilical lymph nodes (Sister Mary Joseph nodule), ovaries (Krukenberg tumor), the left axillary lymph node, and the pouch of Douglas.