see also:

• neoplasia / cancer / tumours
• http://gastro.ucsd.edu/fellowship/Documents/GastriCancer-Dong021610.pdf

• 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 (gastrointestinal stromal tumors (GIST))
• 1% are carcinoid tumour
• 1% are adenoacanthomas
• 1% are squamous cell carcinomas

• 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
• gastric microbiome²⁾
  • risk increased by: Streptococcus anginosus, Fusobacterium nucleatum
  • risk decreased by: Akkermansia muciniphila and various butyrate-producing species
• EBV / glandular fever / infectious mononucleosis
  • is present in 5-15% gastric cancers ?role
• high salt or preserved meat (pickled or smoked) / nitrates intake
• high alcohol intake
• high-fat diets
• 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

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

• gastric cancer can spread by direct invasion, via lymphatics, or hematogenously
• pleural effusion
• ascites
• gastric outlet obstruction
• hepatomegaly
• jaundice (icterus)
• 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

• 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