Stomach Neoplasms

1. Stomach Neoplasms Professor Ravi Kant FRCS (England), FRCS (Ireland), FRCS(Edinburgh), FRCS(Glasgow), MS, DNB, FAMS, FACS, FICS, Professor of Surgery

2. Stomach Neoplasm • Maltoma • Lymphoma • GIST • CA stomach

3. GASTRIC LYMPHOMA

4. Gastric Lymphoma Most common primary GI Lymphoma . It’s increasing in frequency. Presentation: Similar to gastric carcinoma. May reveal peripheral adenopathy, abdominal mass or splenomegaly.

5. Diagnosis: 1.EGD 2.contrast GI x-ray. 3.CT guided fine needle biopsy. Treatment : Gastric Lymphoma Rx is Surgery (Other organs- preferred Rx of Lymphoma is Chemotherapy or Radiotherapy)

6. Maltoma Mucosa associated lymphoid tumour

7. MALTOMA • Aetiology= H Pylori • Rx = Rx of H Pylori • = Triple drugs

8. GIST

15. What are GIST…?? • Gastrointestinal Stromal Tumors are uncommon mesenchymal tumors that arise in the wall of the gastrointestinal tract • It is believed to originate from an intestinal pacemaker cell called the interstitial cell of Cajal.

16. Cajal cell • An intestinal pacemaker cell, has been proposed the cellular origin of GISTs. It has characteristics of both smooth muscle and neural differentiation on ultrastructural examination

18. KIT • role of the KIT and platelet-derived growth factor receptor (PDGFR) tyrosine kinase receptors • KIT receptor tyrosine kinase (KIT RTK)

19. KIT • approximately 5% of GIST cells show not activation and aberrant signaling of the KIT receptor, but rather mutational activation of a structurally related kinase, PDGFR- (PDGFRA). • 90% rate of mutations seen in a more recent series searching for potential mutations in each of exons 11, 9, 13, and 17

22. Diagnosis • CT is the common mode of diagnosis • FDG PET is mandatory ►PET CT scan is ideal • MR

23. GIST & chemoresistance • ▲ P-glycoprotein [the product of the multidrug resistance-1 (MDR-1) gene] • ▲ MDR protein

24. Distribution… • Stomach 50-60% • Small bowel 20-30% • Large bowel 10% • Esophagus 5% • Else where in abdomen 5%

25. Symptoms… • Abdominal pain • Dysphagia • Gastrointestinal bleeding • Symptoms of bowel obstruction • Small tumors may be asymptomatic

26. Cytologically… • Spindle cell GISTs • Epithelioid cell GISTs • Although GISTs can differentiate along either or both cell types, some show NO significant differentiation at all

27. Diagnosis… MUST BE DONE IMMUNOCHEMICALLY • The CD34 antigen (70-78%) • The CD117 antigen (72-94%)

28. Malignant Versus Benign

29. predictors of survival • Male sex, • Tumor size > 5cm • Incomplete resection significant on multivariate analysis

30. Treatment… • Surgical excision is primary treatment option but recurrence rates are high • Resistant to standard chemotherapy regimens due to over-expression of efflux pumps • Radiation therapy limited by large tumor sizes and sensitivity of adjacent bowel

31. IMATINIB • Since activation of Kit played a crucial role in the pathogenesis of GIST, inhibition of Kit would be therapeutic 

32. IMATINIB • Orally bioactive tyrosine kinase inhibitor • Shown to be effective against GIST tumors in two trials in the US and Europe reported in 2001 & 2002

33. Gastrointestinal Stromal Tumor ‘GIST’ Previously leiomyoma & leiomyosarcoma. <1 % Rarely cause bleeding or obstruction. The origin: Intestinal Cells of Cajal ‘ICC;s’ autonomic nervous system. The distinction b\w benign & malignant is unclear. In general terms, the larger the tumor & greater mitotic activity, the more likely to metastases. The stomach is the most common site of GIST.

34. Usually are discovered incidentally on endoscopy or barium meal The endoscopic biopsies may be uninformative as the overlying mucosa is usually normal Small tumorswedge resection Larger onesgastrectomy

37. GIST Rx Surgery Chemoresistance Imatininb Sumanitib Prognosis Predictor factors • Case history-submucosal • Cajal Cell • Gene KIT • PGDRF • Diagnosis • CT • PET

38. GASTRIC CARCINOMA

39. GASTRIC NEOPLASM Epithelial Mesenchymal Benign Malignant • 1.Primary • Adenocarcinoma • Gastrointestinal stromal tumors ‘GIST’ • Lymphoma 2. Secondary: invasion from adjacent tumors.

40. GASTRIC CA

41. Gastric Carcinoma 55 year old Japanese male who is living in Japan & working in industry. Epidemiology & Risk Factors DEFINITION Malignant lesion of the stomach. Incidence of Gastric Carcinoma: Japan 70 in100,000/year Europe 40 in 100,000/year UK 15 in 100,000/year USA 10 in 100,000/year It is decreasing worldwide. Can occur at any age But Peak incidence Is 50-70 years old. It is more aggressive In younger ages. Twice more common In male than in female Studies have confirmed that incidence decline in Japanese immigrant to America. Japan has the world highest Rate of gastric cancer. dust ingestion from a variety of industrial processes may be a risk.

42. Gastric Carcinoma: Risk Factors Environmental: 1.H.pylori infection Sero(+)patients have 6-9 folds risk 2.low socioeconomic Status 3. nationality (JAPAN) 4. Diet (prevention) Predisposing : 1. Pernicious anaemia & atrophic gastritis (achlorhydra) 2. Previous gastric resection 3. Chronic peptic ulcer (give rise to 1%) 4. Smoking. 5. Alcohol. Genetic: 1.Blood group A 2.HNPCC: Hereditary non-polyposis colon cancer.

43. Clinical Presentation Most patients present with advanced stage.. why? They are often asymptomatic in early stages. Common clinical Presentation: The patient complained of loss of appetite that was followed by weight loss of 10Kg in 4 weeks. He had notice epigastric discomfort & postprandial fullness. He presented to the ER complaining of vomiting of large quantities of undigested food & epigastric distension. epigastric pain Bloating early satiety nausea & vomiting* dysphagia* anorexia weight loss upper GI bleeding (hematemesis, melena, iron deficiency anemia) Dyspepsia

44. signs -Anemia. -Wt. loss ( cachexia) -Epigastric mass, Hepatomegaly, Ascitis -Jaundice. -Blumer’s shelf -Virchow's node -Sister Mary Joseph node -Krukenberg tumor -Irish node

45. Pathology DIO Classification Lauren Classification: 1. Intestinal Gastric ca. It arises in areas of intestinal metaplasia to form polypoidtumors or ulcers. 2. Diffuse Gastric ca. It infiltrates deeply in the stomach without forming obvious mass lesions but spreads widely in the gastric wall “LinitisPlastica” & it has much more worse prognosis 3. Mixed Morphology.

46. Morphology • Polypoid • Ulcerative • Superficial spreading • Linitis plastica

47. 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.

48. Staging of gastric cancer Spread of Gastric Cancer Direct Spread Lymphatic spread Tumor penetrates the muscularis, serosa & Adjacent organs (Pancreas,colon &liver) What is important here is Virchow’s node (Trosier’s sign) Blood-borne metastasis Transperitoneal spread This is common Anywhere in peritoneal cavity (Ascitis) Krukenberg tumor (ovaries) Sister Joseph nodule (umbilicus) Usually with extensive Disease where liver 1st Involved then lung & Bone

49. Complications • Peritoneal and pleural effusion • Obstruction of gastric outlet or small bowel • Bleeding • Intrahepatic jaundice by hepatomegaly

50. Differential Diagnosis 1.Gastric ulcer 2.Other gastric neoplasms 3.Gastritis 4.Gastric Polyp 5.Crohns disease. From history, Cancer is not relieved by antacids Not periodic Not relieved by eating or vomiting.