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neo_gastric

stomach cancer

introduction

  • 2nd most common cause of cancer-related death in the world
  • remains difficult to cure as most present late
  • 14th most common cancer in Western cultures and ranks about 7th in cancer causes of mortality, and median age at Dx is around 70yrs, with 25% present with localized disease, 31% with regional disease, 32% with metastatic disease
  • 40% of cancers develop in the lower part, 40% in the middle part, and 15% in the upper part
  • 90-95% of all gastric malignancies are adenocarcinoma of the stomach
    • pre-malignant phases:
      • chronic atrophic gastritis is the first histopathologic lesion of the preneoplastic cascade
      • intestinal metaplasia
      • dysplasia
  • 1-5% are lymphoma
  • 2% are gastrointestinal stromal tumors
  • 1% are adenoacanthomas
  • 1% are squamous cell carcinomas

risk factors

  • high prevalence in Japan, Andean regions of South America, and Eastern Europe
  • diet vs genetics
    • early environmental exposure, rather than genetic factors, appear to have a greater influence on risk
    • 10% are familial (independent of H.pylori infection)
    • diffuse type – strongly correlated with mutations in E-cadherin gene, CDH1
      • risk for people carrying these rare mutations in the E-cadherin gene have 70% chance if male and 56% if female (and these woman also have 42% chance of lobular breast cancer 1)
    • hereditary syndromes:
      • HNPCC, FAP, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, Cowdens syndrome
  • chronic Helicobacter pylori infection
    • the strongest risk factor
    • 3 cases per year for every 10,000 infected persons
    • is present in 5-15% gastric cancers ?role
  • high salt or preserved meat (pickled or smoked) / nitrates intake
  • contamination of food by carcinogenic compounds arising from the decay of unrefrigerated meat products
  • hypochlorhydria (chronic atrophic gastritis, pernicious anaemia, partial gastrectomy)
    • ⇒ decrease in luminal vitamin C, which is an antioxidant
    • ⇒ increase in serum gastrin, which is a potent inducer of gastric epithelial cell proliferation
    • ⇒ allows colonization of bacteria capable of converting dietary nitrates to mutagenic N-nitroso compounds
    • BUT notably, chronic hypochlorhydria induced by H2 blockers or proton pump inhibitors (PPIs) does not lead to increased risk of cancer
  • gastric polyps
  • gastric ulcers
  • smoking
  • obesity - increases risk of gastric cardia cancers
  • blood group A patients are at 20% excess risk of cancer
  • Various immunodeficiency syndromes
  • Menetrier disease
  • reproductive hormones are thought to have a protective role (risk is lower in women)
  • Hereditary Diffuse Gastric Cancer
    • AD with very high penetrance giving lifetime risk of 40-67% in men and 60-83% in women
    • average age at Dx is 38yrs
    • affected women are also at increased risk of lobular breast cancer

clinical features

  • asymptomatic
  • indigestion or fullness
  • anorexia, nausea or vomiting
  • dysphagia
  • LOW
  • palpable enlarged stomach with succusion splash
  • lymphadenopathy, particularly left supraclavicular (Virchow node), anterior axillary, periumbilical nodes

other late complications

  • gastric cancer can spread by direct invasion, via lymphatics, or hematogenously
  • pleural effusion
  • ascites
  • gastric outlet obstruction
  • cachexia
  • Krukenberg tumor – metastatic tumor to the ovary
  • paraneoplastic syndromes:
    • sign of Leser-Trelat – sudden appearance of diffuse seborrheic keratoses
    • dermatomyositis
    • acanthosis nigricans
    • circinate erythema

investigations

  • gastroscopy and biopsy
  • CEA is elevated in about 50% of cases
  • CA 19-9 is elevated in about 20% of cases
  • CT abdo to assess extent of local disease and spread
1)
Guilford et al, JAMA Oncology 2015
neo_gastric.txt · Last modified: 2015/02/14 10:52 (external edit)