symposium on carcinoma of the stomach.pptx

epidemiology of cancer stomach

1. Carcinoma stomach- Symposium Dr Sunil Krishna M Assistant Professor Department of General Surgery KMC Manipal

2. Incidence and epidemiology 875000 new cases world wide per year Worldwide fourth most common cancer and second leading cause of cancer death Prevalent in East Asia and South America highest 30 to 85 per 100000 population and lowest 4 to 8 per 100000 population Commonest cancer in Japan Gender- more common in men. Age- Most people diagnosed with stomach cancer are between their late 60s and 80s

3. Adenocarcinoma-85% Site- 40% lower part, 40% body of stomach, 15 % upper part , 10% multiple sites Highest mortality rate in Eastern asia Sporadic -90-92% Familial- 5-6% Inherited cancer predisposition syndrome- 1-2%

4. Etiopathogenesis H pylori- long term infection with bacteria leads to gastritis chronic inflammation Gastric atrophy Intestinal metaplasia molecular alteration Dysplasia Intestinal adenocarcinoma

5. Molecular alteration in H pylori infection- Overexpression of cyclooxygenase 2 and cyclin D2 P53 mutations, Microsatellite instability Decreased p27 expression and alteration in transcription factors such as CDX1 and CDX2 Intestinal metaplasia with high levels of interleukin 1 expression are at increased risk of gastric cancer Cytoxan associated gene A ( cag A ) positive H pylori infection high rates

6. Patient with MALT lymphoma increased risk for ca stomach Epstein-Barr virus (EBV)- 5% to 10% of people with stomach cancer. Slow growing, less aggressive cancer with a lower tendency to spread. ??Risk factor Tobacco smoking- Risk of proximal ca stomach Type A blood group – risk..??? Workers in the coal, metal, rubber industries Immuno deficiency- risk of chronic atrophic gastritis

7. Dietary factors High salt food such as salted or smoked meats contains high levels of nitrate along with low fruit and vegetable intake Mechanism- conversion of nitrates in the food to N- nitroso compounds by bacteria in the stomach. carcinogenic Fresh fruits vegetables contain ascorbic acid which removes N nitroso compounds Synergism of risk factors between H pylori and dietary factors- H pylori has been shown to promote the growth of the bacteria that generate carcinogenic N – nitrosocompound H pylori also inhibits the secretion of ascorbic acid

8. Previous stomach surgery- surgery for non cancerous disease. Less acid secretion which allows more nitrite-producing bacteria to be present. Reflux of bile from the small intestine into the stomach after surgery might also add to the increased risk. These cancers typically develop many years after the surgery

9. Pernicious anemia- Achlorhydria occurs due to destruction of chief and parietal cells by autoimmune reaction. Menetrier disease (hypertrophic gastropathy) In this condition, giant fold of the stomach, gastric gland atrophy and hypochlorhydria, hypoalbuminemia. Antral sparing Polyps- Adenomatous polyp – 10 to 20 % risk and risk increases with size Sessile, larger than 2cm Hyperplastic and inflammatory polyps no risk

10. Hereditary risk factors and cancer genetics E- cadherin gene mutation- 80% lifetime incidence of developing gastric ca. Hereditary diffuse gastric cancer…? Role of prophylactic gastrectomy. FAP- 85% have fundic gland polyps with over 50 % somatic adenomatous polyposis coli mutation. Mutation in APC gene Li fraumeni syndrome- autosomal dominant, mutation in tumor suppressor gene p53 HNPCC( lynch syndrome) incresed risk of gastric cancer due to microsatellite instability in MLH1 or MSH2 gene Hereditary diffuse gastric cancer. Associated with breast cancer in women due to mutation in CDH1 gene

11. BRCA1 or BRCA2 may also have a higher rate of stomach cancer. Several genetic alteration associated with gastric ca. Peutz-Jeghers syndrome (PJS) increased risk of cancers of the breast, colon, pancreas, stomach. Mutation in the gene STK1. A family history of stomach cancer People with first-degree relatives (parents, siblings, or children).

12. Activation of oncogenes, inactivation of tumor suppressor genes, reduction of cellular adhesions, reactivation of telomerase and presence of microsatellite instability. Over expression of c-met, k-sam, c-erbB2 oncogenes Inactivation of p53 and p16 genes in diffuse and intestinal type of cancers Microsatellite instability seen in intestinal type of gastric ca

13. Precancerous conditions Chronic atrophic gastritis Pernicious anemia Intestinal metaplasia Chronic gastric ulcer Menetriers disease Gastric polyp

14. Pathological types Lauren’s classification- Based on histology 1. Intestinal Gastric ca. It arises in areas of intestinal metaplasia to form polypoid tumors or ulcers . 2. Diffuse Gastric ca. It infiltrates deeply in the stomach without forming obvious mass lesions but spreads widely in the gastric wall “Linitis Plastica” & it has much more worse prognosis 3. Mixed Morphology.

15. Based on endoscopic finding of depth of invasion classified into Japanes and Borrmann classification Protruded, superficial, excavated Borrman- polypoidal, ulcerated, ulcerated infiltrating , diffuse infiltrating

16. Gastric cancer can be divided into: Early: Limited to mucosa & submucosa with or without LN (T1, any N) curable with 5 years survival rate in 90%. Advanced: It involves the Muscularis. It has 4 types( Bormann’s classification). Type III & IV are incurable.

17. NCCN criteria for risk evaluation A known mutation in a gastric susceptibility gene in the family Gastric cancer in one family member before age 40 or Gastric cancer in 2 first/second degree relative with one before age 50 or Gastric cancer in 3 first/second degree relatives with independent of age Gastric caner and breast cancer in one patient with one diagnosed before 40 or Gastric cancer in one and breast cancer in first /second relative with one diagnosis before age 50

18. Factors Associated with Increased Risk of Developing Stomach Cancer Acquired factors Nutritional    High salt consumption    High nitrate consumption    Low dietary vitamin A and C    Poor food preparation (smoked, salt cured)    Lack of refrigeration    Poor drinking water (well water) Occupational    Rubber workers    Coal workers Cigarette smoking Helicobacter pylori infection Epstein-Barr virus Radiation exposure Prior gastric surgery for benign gastric ulcer disease Genetic factors    Type A blood    Pernicious anemia    Family history    Hereditary nonpolyposis colon cancer    Li-Fraumeni syndrome Precursor lesions     Adenomatous gastric polyps    Chronic atrophic gastritis    Dysplasia    Intestinal metaplasia    Menetrier's disease

19. Thank you