Gastric tumors can be benign or malignant. The most common malignant tumors are adenocarcinoma, lymphoma, and gastrointestinal stromal tumor (GIST). Risk factors for gastric cancer include H. pylori infection, diet, genetics, and conditions causing gastric atrophy. Early detection of gastric cancer improves survival rates. Treatment depends on the stage but may involve surgery, chemotherapy, and radiation therapy. Gastric lymphoma is usually non-Hodgkin's lymphoma and has a better prognosis than adenocarcinoma. GIST tumors originate in the stomach wall and can be benign or malignant depending on size and other characteristics.

1. Gastric tumors: Benign : Polyps Lieomyoma (Gastrointestinal stromal tumor GIST ) Malignant : Adenocarcinoma 85% Lymphoma 5% GIST Sarcoma Carcinoid Others

3. Gastric polyps: Hyperplastic – Benign, inflammatory,hamartomas 75% Adenomatous – Premalignant Mixed Part of FAP syndrome

4. Gastric Cancer Gastric cancer Adenocarcinoma GIST (gastro-intestinal stromal tumour) Carcinoid Lymphoma other

5. Pathohistologic classification Histology Adenocarcinoma 90% Lymphoma 5% GI Stromal tumor 2% Carcinoid <1% Metastasis <1% Adenosquamous/squamous <1% Miscellaneous <1%

6. Adenocarcinoma – Lauren classification Diffuse Linitis plastica type Poorer prognosis Intestinal Localised Better prognosis Distal stomach

7. Gastric Cancer: Adenocarcinoma 750,000 cases annually. 22,000 new cases in the US each year Rise in cancer of the proximal stomach and GEJ

8. Risk Factors Diet Genetics H. Pylori infection: very important cause. Pernicious anemia Pts with partial gastrectomy Vagotomy. Atrophic gastritis Menetrier’s disease

9. Risk Factors Dietary Factors- foods rich in nitrates, nitrites, preserved meat & vegetables(smoked/salted). Genetic Factors - Lynch syndrome II. Microsatellite instability (MSI) is present in up to 33% of gastric cancers Pernicious Anemia - auto-immune atrophic gastritis increased risk by 2-3x

10. Risk Factors Partial gastrectomy- slightly increased risk Menetrier’s Disease - rugal fold hypertrophy, hypochlorhydria and protein-losing enteropathy Adenomatous Gastric Polyps

11. Gastric Cancer Environmental factors H. pylori Genetic factors Etiological Factors of Gastric Cancer Precancerous changes

12. Pathologic Features Distal cancer- H. Pylori related Proximal cancer- GERD/Barrett’s dz Chronic gastritis  Atrophic Gastritis  Intestinal Metaplasia  Dysplasia/Cancer Intestinal type vs diffuse type

13. Gastric Cancer

14. Clinical Features Vague symptoms- early satiety, abdominal pain, bloating, dyspepsia, wt loss, anorexia GI bleeding, microcytic anemia, vomiting if GOO present Associated paraneoplastic syndromes- Acanthosis Nigricans Venous Thrombi (Trousseau’s syndrome) Metastasis: Sister Mary Joseph’s node Virchow’s node Liver secondaries.

15. Clinical manifestation Signs/Symptoms of Early Gastric Cancer Asymptomatic or silent 80% Peptic ulcer symptoms 10% Nausea or vomiting 8% Anorexia 8% Early satiety 5% Abdominal pain 2% Gastrointestinal blood loss <2% Weight loss <2% Dysphagia <1%

16. Signs and Symptoms Advanced Gastric Cancer Weight loss 60% Abdominal pain 50% Nausea or vomiting 30% Anorexia 30% Dysphagia 25% Gastrointestinal blood loss 20% Early satiety 20% Peptic ulcer symptoms 20% Abdominal mass or fullness 5% Asymptomatic or silent <5% Duration of symptoms Less than 3 month 40% 3-12 months 40% Longer than 12 month 20%

17. Special signs & terms Linitis plastica: diffusely infiltrating with a rigid stomach Virchow’s node: supraclavicular lymphadenopathy (left) Irish’s node: axillary lymphadenopathy Sister Mary Joseph’s node: umbilical lymphadenopathy

18. Laboratory tests Iron deficiency anemia Fecal occult blood test (FOBT) Tumor markers (CEA, Ca19-9)

19. Diagnostic Studies Contrast radiograpy( Barium) - may be initial test for vague symptoms. Endoscopy: the usual diagnostic method with the use of image enhancing methods as chromo endoscopy for early detection of small lesions. CT - cannot determine depth of invasion. Good for detecting distant disease EUS - more accurate for T / N staging than CT

20. Staging/Prognosis Early gastric cancer- 5-yr survival rate of 80-90% Survival for Stage III or IV disease is 5-20% at 5 years

21. T stage (UICC TNM 2002) T1 T3 T2b T2a T1 Adjacent structure T4

22. N & M stage (UICC TNM 2002) N stage N0 - no nodes N1 - 1-6 nodes N2 - 7-15 nodes N3 > 15 nodes M stage M0 – no distant metastases M1 – distant metastases (includes distant nodes

24. Early GC: Incidence of EGC increased from 1-15% Due to Open access endoscopy For early diagnosis urgent (<2 weeks) specialist referral for endoscopic investigation indicated when dyspepsia with: Chronic GI bleeding Progressive unintentional wt loss Progressive dysphagia Persistent vomiting Iron deficiency anaemia Epigastric mass Suspicious barium meal

25. Early GC: Mostly Japanese. Confined to the mucosa &submucosa, irrespective of nodal state, Surgical resection may be curative &definitely improves the 5-year survival rate to > 50%. When early gastric cancer is confined to the mucosa, endoscopic mucosal resection (EMR) may be an alternative.

26. Treatment The only chance for cure is surgical resection, possible in 25-30%. If confined to the distal stomach, subtotal gastrectomy with resection of lymph nodes in the porta hepatis & pancreatic head. In tumors of the proximal stomach total gastrectomy to obtain an adequate margin & to remove lymph nodes+ distal pancreatectomy &splenectomy, but with higher mortality/ morbidity. Limited gastric resection is necessary for patients with excessive bleeding or obstruction& If cancer recurs in the gastric remnant. 66% present with advanced disease incurable by surgery alone Resistant to radiotherapy- used mostly for palliation Chemo- decreases tumor burden in 15% of patients at best

27. Gastric lymphoma: M ost of B-cell origin Primary gastric lymphoma rare Non-Hodgkin’s most common type 5 year survival rate is 50%

28. Gastric lymphoma: 5% of all malignant gastric tumors. Increasing in incidence. The majority are non-Hodgkin’s lymphomas & the stomach is the most common extranodal site for non-Hodgkin’s lymphomas. Generally younger than those with gastric adenocarcinoma,also male predominance. Commonly present with symptoms & signs similar to adenoca. Lymphoma in the stomach can be a primary tumor or can be due to disseminated lymphoma. B-cell lymphomas of the stomach are most commonly large cell with a high-grade type. Low-grade variants are noted in the setting of chronic gastritis called mucosa-associated lymphoid tissue (MALT) lymphomas. strongly associated with H. pylori infection.

29. Gastric lymphoma: diagnosis Ba: usually ulcers or exophytic masses; a diffusely infiltrating lymphoma is more suggestive of secondary lymphoma. Primary gastric lymphoma, Barium usually show multiple nodules& ulcers. Secondary lymphoma typically have the appearance of linitis plastica. UGI endoscopy with biopsy/cytology are required for diagnosis with accuracy of 90%. Conventional histopathology& immunoperoxidase staining for lymphocyte markers is helpful in diagnosis. Proper staging of gastric lymphoma involves EUS, chest& abdominal CT scans& bone marrow biopsy.

30. Gastric lymphoma: Treatment Treatment of gastric diffuse large B-cell lymphoma is best pursued with combination chemotherapy with or without radiotherapy with 5-year survival rates of 40-60%. For MALT lesions, eradication of H. pylori with antibiotics induces regression of the tumor, but longer term follow-up is needed. Radiotherapy can be curative for localized MALT lymphomas.

31. MALTomas Low grade B-cell lymphoma associated with chronic H. Pylori infection EUS is most reliable method for staging Treatment of H. Pylori eradicates the tumor

32. Other Gastric Tumors GIST - originate usually from the muscularis propria. Carcinoid Tumors - 0.3% of all gastric tumors. Produce 5-HIAA and can cause carcinoid syndrome. May lead to hyper-gastrinemia

33. GIST: Gastro Intestinal Stromal Tumors Around 5,000 to 6,000 new cases each year Tends to occur in middle aged persons with a slight male predilection Occur throughout the GI tract

34. GIST: Stomach 50-60% Small bowel 20-30% Large bowel 10% Esophagus 5% Else where in abdomen 5% Symptoms depend on the site& size of the tumor: Abdominal pain Dysphagia Gastrointestinal bleeding Symptoms of bowel obstruction Small tumors may be asymptomatic Diagnosis: Light microscopy with Immuno-histochemistry

35. GIST: Features favoring benign lesions in general like: Size less than 5 cm Low number of mitosis per HPF No mucosal invasion Low cellularity Low markers of cell proliferation The above have shown to be associated with malignant behavior in some but not in other studies. With prolonged follow up any GIST has the potential to behave in a malignant fashion. 50% of primary localized tumors that are resected relapse after 5 years of follow up.

36. Malignant Versus Benign Size Mitotic count Very Low risk <2 cm <5/50 HPF Low risk 2-5 cm <5/50 HPF Intermediate risk <5 cm 5-10 cm 6-10/50 HPF <5/50 HPF High risk >5 cm >10 cm Any size >5/50 HPF Any count >10/50 HPF

37. Since activation of Kit played a crucial role in the pathogenesis of GIST, inhibition of Kit would be therapeutic. Imatinib was found to be effective in GIST. Indicated for large tumors pre or postoperative.

38. Prognosis: The 5-year survival for malignant GIST varies widely from 28 to 80%. Median survival of patients in whom complete surgical resection is not possible is 10–23 months. The median survival from the time of diagnosis of metastatic or recurrent disease has been reported from 12 to 19 months.

39. Gastric carcinoids: Relatively uncommon. They are grouped into three categories Type 1: gastric carcinoids are associated with chronic atrophic gastritis and often pernicious anemia they account for 70 to 80 percent of all gastric carcinoids. Type 2 occur in association with gastrinomas (Zollinger-Ellison syndrome) MEN type 1. They account for <5% of gastric carcinoids. Similar to carcinoids in atrophic gastritis, the tumors are thought to arise from ECL cells. Type 3 known as sporadic carcinoids occur in the absence of atrophic gastritis or ZES or MEN-1 syndromes. Account for 20 % of gastric carcinoids, are the most aggressive; local or hepatic metastases are present in up to 65 % who come to resection.

40. Gastric cancers

41. Endoscopic features of gastric cancer

42. EUS-Stomach