1. Pathology of the stomach. Ileus. Vascular diseases of the bowels and the peritoneum. PATHOLOGY OF THE STOMACH Stomach mucosa • Gastric mucosa is covered by a layer of mucus. The mucosal glands comprise the cardiac glands, the fundic glands in the fundus and body of the stomach, and the pyloric glands in the antrum. • The surface mucous cells and the cardiac and pyloric glands secrete mucus which protects the stomach from self- digestion. • In fundic glands, the chief cells secrete pepsinogen; the parietal cells secrete HCl, bicarbonate, and intrinsic factor, and the endocrine cells release histamine. • Pyloric endocrine cells secrete gastrin, somatostatine, etc. Glossary • Gastritis - inflammation of the gastric mucosa associated with gastric mucosal injury • Gastropathy - epithelial cell damage and regeneration without associated inflammation • Erosion - circumscribed necrosis-induced defect of mucosa that does not cross the muscularis mucosae • Ulcer - the defect extends beyond the mucosa ACUTE GASTRITIS Pathogenesis Common condition, induced by acute damage to the gastric mucosa due to • alcohol, NSAIDs (nonsteroidal anti-inflammatory drugs, e.g., aspirin) or steroids • stress situations, e.g., severe burns, hypothermia, shock, CNS trauma, etc. • Helicobacter pylori infection Pathological features • Hemorrhagic-erosive inflammation of gastric mucosa affecting the entire stomach (pangastritis) or the antrum of stomach (antral gastritis) • Mucosal hyperemia, punctate hemorrhages, multiple erosions • + Acute ulcers: anywhere in the stomach (rarely in the proximal duodenum); multiple, <1 cm; usually do not penetrate through the muscularis propria layer • Healing is complete Clinical features • Epigastric pain, nausea, vomiting • On occasion, massive bleeding with hematemesis and melena ± hemorrhagic shock • Dg.: via endoscopy of stomach CHRONIC GASTRITIS • Common features: atrophy of the gastric mucosa and metaplastic transformation of the gastric glands Helicobacter pylori-induced gastritis (also termed as environmental metaplastic atrophic gastritis; EMAG) • Very common; in the absence of antibiotic therapy, it persists for life • Diagnosed histologically in biopsy samples obtained endoscopically • Associated with increased risk of peptic ulcer, gastric adenocarcinoma, and gastric MALT-lymphoma • HP eradication therapies reduce the risk of these pathologies Pathogenesis • HP microbes colonize on and injure the mucous cells • HP is protected from the acidic gastric juice because the microbes produce urease; the ammonia and bicarbonate produced neutralize the acid Morphology • Chronic active gastritis, most marked in the antrum • Gram-negative, spiral-shaped bacilli are attached to the mucous cells; infiltration of the lamina propria by lymphocytes and plasma cells + lymphoid follicles; neutrophilic infiltration of the mucous neck region • Longstanding inflammation: multifocal mucosal atrophy, characterized by loss of specialized cells in gastric glands, and their metaplastic replacement by columnar absorptive cells and goblet cells (intestinal metaplasia); fibrosis of the lamina propria; + dysplasia (intraepithelial neoplasia) in the glands Clinical features • No symptoms or epigastric discomfort • Patients with antral predominant gastritis have increased gastrin release and reduced somatostatin release → high HCl production → frequent development of duodenal peptic ulcer • Patients with multifocal atrophic gastritis have decreased acid production, may develop gastric peptic ulcers and have an increased risk for gastric adenocarcinoma Autoimmune metaplastic atrophic gastritis (AMAG) Pathogenesis • Rare • Autoantibodies to the gastric parietal cells. Can be isolated or associated with other autoimmune disorders Morphology Chronic atrophic corpus gastritis: lymphoplasmocytic infiltration of the lamina propria, extensive loss of the parietal cells, and intestinal metaplasia in the glands; + dysplasia (intraepithelial neoplasia) in the glands • Antrum: G-cell hyperplasia Clinical features • Reduced acid secretion: hypochlorhydria • Hypergastrinemia: response to hypochlorhydria to stimulate HCl production in the vanishing parietal cells • Intrinsic factor is not produced → disturbed vitamin B12 absorption → pernicious anemia • High risk for the development of gastric adenocarcinoma 1 1. Pathology of the stomach. Ileus. Vascular diseases of the bowels and the peritoneum. Reactive gastropathy • Frequent condition Pathogenesis • Reflux of bilious duodenal secretions or long-term usage of NSAIDs Morphology • The chemicals cause foveolar hyperplasia, mucosal edema, congestion of capillaries, and smooth muscle proliferation in the lamina propria • No significant increase in chronic inflammatory cells Clinical features • Mild dyspepsia + epigastric pain CHRONIC PEPTIC ULCER DISEASE Pathogenesis • Most ulcers are caused by HP infection or drugs (NSAID, steroids), both factors disrupt normal mucosal defense and repair, making the mucosa more susceptible to acid and pepsin • Other ulcerogenic effects: smoking, hypergastrinemia, emotional stress • Duodenal ulcer: increased production of gastric acid and HP-gastritis. The mechanism by which HP promotes duodenal ulcerogenesis is not known. Location • Stomach, usually the antrum and the lesser curvature • Postpyloric duodenum: in the first 2 cm-s distal to the pylorus on the anterior or posterior wall. • Within Barrett’s mucosa in esophagus Gross • Single, sharply demarcated round ulcer 1 to 2.5 cm in diameter • Healing: epithelium covers the defect, the smooth muscle cells do NOT regenerate, fibrosis takes place at the site of the injury Clinical features • Epigastrial pain releaved by food or antacids Complications Gastric ulcer • Mild to severe hemorrhage from eroded vessels • Perforation peritonitis • Pyloric stenosis due to the progressive shrinkage of fibrotic tissue proximal stomach becomes greatly dilated; persistent vomiting • Malignant change Duodenal ulcer • Penetration into the pancreas • Profuse bleeding from erosion of branches of the superior pancreatico-duodenal artery hemorrhagic shock • Perforation peritonitis • No risk of malignant transformation Good news: complex therapy has decreased advanced peptic ulcer disease (eradication of H. pylori infection, proton pump inhibitor treatment of hyperacidity, and modification of lifestyle) Acute upper gastrointestinal bleeding - summary Symptoms • Hematemesis - vomiting of blood • Melena – passage of black tarry stools • On occasion: hemorrhagic shock - life-threatening condition: pallor, cold nose, systolic BP below 100 mmHg, pulse above 100 b.p.m Common causes • Esophageal varices • Mallory-Weiss sy • Chronic peptic ulcer of duodenum or stomach • Acute erosive/hemorrhagic gastritis GASTRIC EPITHELIAL TUMORS Benign Hyperplastic (regenerative) polyps • Non-neoplastic small, often multiple polyps; mostly in the antrum • Seen in the setting of chronic gastritis Intestinal-type adenoma • Strong potential for malignant change • Gross: solitary polyp, greater than 1 cm; mainly in the antrum • LM: proliferation of dysplastic tubules that form polyp Clinical features • Extensive metaplastic atrophic gastritis mostly coexists • Mainly asymptomatic; recurrent bleeding of large adenomas may result in anemia Malignant Adenocarcinoma • High incidence in central and eastern Asia, eastern Europe, South America 2 1. Pathology of the stomach. Ileus. Vascular diseases of the bowels and the peritoneum. • Peak: between 50-60 ys Etiology • Multifactorial • 90% of cases - sporadic, 10% - familial/hereditary • Environmental factors: H. pylori infection, EBV infection, tobacco smoking, and diet high in smoked and/or salt- preserved foods and low in fruits and vegetables Anatomical location • Usually along the lesser curvature of the antropyloric region • Less common: cardia Gross Early carcinomas • Polypoid (>3 mm) or flat lesions in the form of mucosal patches or a loss of rugae • May not be recognized on endoscopy Advanced carcinomas • Localized growth with a fungating or ulcerated appearance • Infiltrative growth with or without ulceration • Linitis plastica (tube-like alteration of the stomach): no obvious tumour mass is visible on the mucosal surface; however, the gastric wall becomes thickened by the tumorous infiltration Histological and molecular features, and prognosis 1) Intestinal adenocarcinomas • Well or moderately differentiated; form tubular structures reminiscent of adenocarcinomas of colon • Chromosomally instable tumors; display DNA aneuploidy, translocations, and mutations in proto-oncogens (receptor tyrosine kinase-RAS activation) and tumor suppressor genes (TP53) • Better prognosis than the diffuse type 2) Diffuse carcinomas • Poorly differentiated; composed of poorly cohesive tumor cells or signet-ring cells; desmoplastic reaction leads to linitis plastica • Genomically stable tumors; display epithelial-cadherin gene (CDH1) mutations or RHOA mutations • Highly malignant; poor prognosis 3) Other histological subtypes • Microsatellite instabile tumors, or positive for Epstein-Barr virus Patterns of spread • Directly to the serosa; local invasion of the duodenum, pancreas, and retroperitoneum • Peritoneal dissemination: carcinosis of peritoneum • Lymphatic metastases: local lymph nodes; Virchow node: supraclavicular lymph node • Retrograde lymphatic spread: signet-ring carcinoma metastasis to both ovaries (Krukenberg tumor) • Hematogeneous metastases: liver Stage Early carcinoma • Invades no more deeply than the submucosa,