Chronic Gastritis and Gastric Cancer Thomas Rosenzweig, MD

Chronic Gastritis H. pylori = most common cause spiral-shaped or curved bacilli fecal-oral Intra-epithelial neutrophils and sub-epithelial plasma cells Autoimmune gastritis = most common form of chronic gastritis in patients without H. pylori infection diffuse mucosal damage of the oxyntic (acid-producing) mucosa in the body and fundus spares the antrum associated with hypergastrinemia 60 year old women Symptoms: nausea and upper abdominal pain Complication: Peptic ulcer disease (PUD) chronic mucosal ulceration affecting the duodenum or stomach H. pylori infection, NSAIDs, or cigarette smoking Most common: H. pylori-induced antral gastritis in gastric antrum or duodenum ↑ gastric acid secretion ↓ decreased duodenal bicarbonate secretion

Helicobacter pylori Gastritis H. pylori infection antral gastritis ↑ acid production risk of duodenal peptic ulcer. Intra-epithelial neutrophils and sub-epithelial plasma cells May involve the gastric body and fundus multifocal atrophic gastritis ↓ Decreased acid production risk of gastric adenocarcinoma Inverse relationship between duodenal ulcer and gastric adenocarcinoma

Helicobacter pylori Gastritis H. pylori Flagella (can move in mucus) Urease (↑ gastric pH) Adhesins (attach surface foveolar cells) Toxins (cytotoxin-associated gene A (CagA)) Atrophic mucosa ↓ parietal and chief cells mucosa-associated lymphoid tissue (MALT) B-cell lymphoma risk Treatment antibiotics proton pump inhibitors

Autoimmune Gastritis intestinal metaplasia ↓ parietal cells (killed by CD4+ T cells) ↓ gastric acid (negative feedback gone) ↑gastrin release (nothing to stop it) Hypergastrinemia Hyperplasia of antral gastrin-producing G cells ↓ intrinsic factor ↓ ileal vitamin B12 absorption pernicious anemia intestinal metaplasia Goblet cells Associated with Oxyntic atrophy ↑ risk of gastric adenocarcinoma Risk is greatest in autoimmune gastritis

Gastritis Comparison Table

Key Concepts

Gastric Polyps and Tumors

1. Inflammatory (Hyperplastic) Polyps Most polyps H. pylori infection associated with chronic gastritis irregular, cystically dilated, and elongated foveolar glands 2. Fundic Gland Polyps occur in the gastric body and fundus irregular glands lined by flattened parietal and chief cells sporadically no cancer risk individuals with familial adenomatous polyposis (FAP) Dysplasia and even cancer More common due to proton pump inhibitor therapy ↓ acid production → ↑ gastrin secretion → ↑ oxyntic gland growth 3. Gastric Adenoma 50 and 60 year old males In the antrum Risk of adenocarcinoma in lesions greater than 2 cm in diameter Pt. likely has chronic gastritis with atrophy and intestinal metaplasia Risk of cancer is much higher in gastric adenomas than in intestinal adenomas.

Gastric Adenocarcinoma ***Most common*** Intestinal type Bulky masses (glands) ↑ signaling via the Wnt pathway Diffuse type Signet ring cells (mucin vacuoles) ↓ CDH1 (↓ E-cadherin) Familial gastric cancer Half of sporadic cases Linitis plastica (leather bottle appearance)

Gastric Adenocarcinoma Morphology Intestinal Type Japan, Chile, Costa Rica, and Eastern Europe develops from precursor lesions male-to-female ratio is 2 : 1. Pts. with multifocal mucosal atrophy and intestinal metaplasia Diffuse Type is relatively uniform across countries, no precursor lesions males and females are equally affected 5-year survival is less than 30%. involves the gastric antrum and the lesser curvature

Key Concepts