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  1. 1. Case History<br />66 year old man complains of:<br />Epigastric pain which has gradually increased for the past two months<br />Loss of appetite (anorexia)<br />Early satiety<br />Weight loss of 5 kilos<br />Vomited twice in the past week<br />
  2. 2. Case History <br />Black bowel movements for 2 days three weeks previously (melena) <br />Wakes at night with pain<br />Took aspirin for pain<br />Weak<br />
  3. 3. Objective Findings<br />Physical examination: <br />fullness and tenderness in the epigastrium<br />Lab<br />Hemoglobin 11.6 g/dl, MCV 68, Fe 26 (low)<br />
  4. 4. Doc – What’s wrong with me?(Have I got Cancer?)<br />
  5. 5. Clinical Approach<br />
  6. 6. Differential DiagnosisBenign Disease<br />Peptic Ulcer Disease<br />Gastritis, gastric ulcer, duodenitis, duodenal ulcer<br />Hepatobiliary disease<br />Gallstone disease<br />Pancreatic disease<br />Pancreatitis – acute, chronic, <br />
  7. 7. Differential DiagnosisMalignant Disease<br />Gastric tumor <br />Adenocarcinoma, lymphoma, Gastrointestinal Stromal Tumors (GIST), leiomyosarcoma, neuroendocrine <br />Liver and bile ducts<br />Primary, secondary liver tumors, cholangiocarcinoma, gallbladder cancer<br />Pancreas<br />Adenocarcinoma solid (>80%) or cystic (5%), neuroendocrine<br />
  8. 8. Alarm Symptoms<br />Age >50y<br />Increasing abdominal pain, <br />Wakes at night <br />Anorexia, Weight loss<br />Early satiety<br />Anemia<br />Conclusion: Urgent Investigation<br />
  9. 9. Gastric Tumors<br />5 main types: <br />Adenocarcinoma: This is the most common type of stomach cancer, 90 to 95 percent of stomach cancer cases, and develops in the glandular tissues. <br />Lymphoma: Develops in lymphatic tissue of the stomach wall – about 5% of tumors.<br />Carcinoid Tumors: Develops in the hormone-producing tissues of the stomach. Most of these tumors do not spread to other organs – 3%. <br />Gastrointestinal Stomal Tumors (GIST): Develops in the stomach wall tissues that contain a specific type of cell called intestinal cells of Cajal. Gastrointestinal stomal tumors are a rare form of cancer and can occur anywhere in the gastrointestinal tract. However the majority of GIST cases occur in stomach – 2%. <br />Leiomyosarcoma: Develops in the stomach muscle layer 1%.<br />
  10. 10. Epidemiology of Gastric Adenocarcinoma<br />
  11. 11. Gastric Carcinoma Epidemiology<br />
  12. 12. Gastric Adenocarcinoma-Epidemiology<br />Incidence and mortality decreasing<br />Risk greater in lower socioeconomic classes<br />Migrants from high to low-incidence nations maintain their susceptibility to gastric cancer<br />Migrant offspring approximates that of the new homeland<br />Environmental exposure early in life<br />Dietary carcinogens<br />
  13. 13. Pathogenesis of Gastric Cancer<br />Environmental<br />(intestinal type)<br />Helicobacter pylori<br />Diet <br />High concentrations of nitrates in dried, smoked, and salted foods<br />Smoking<br />Surgery to control benign peptic ulcer disease<br />Adenomatous polyps<br />Ménétrier's disease<br />Genetic<br />(diffuse type)<br />Familial adenomatouspolyposis (FAP) <br />Hereditary nonpolyposis colorectal cancer (HNPCC) <br />E-cadherin mutations, <br />IL1βpoymorphism<br />Blood group A<br />
  14. 14. Multistep Pathway in the Pathogenesis of Gastric Cancer <br />
  15. 15. Helicobacter and Gastric Cancer<br />36/1246H. pylori positive 0/280 negative patients developed gastric cancer<br />
  16. 16. Gastric Cancer - Diagnosis<br />Investigations<br />Barium studies<br />Upper gastrointestinal gastroscopy<br />CT scan<br />Endoscopic ultrasound (EUS)<br />Tumor markers - blood<br />
  17. 17. Normal Barium Study<br />Gastric fundus<br />Gastric body<br />Duodenal cap<br />Pylorus<br />Gastric antrum<br />Duodenum-2nd part<br />
  18. 18. Tumor<br />Gastric antrum<br />Barium Contrast Upper GI Series Gastric Cancer - Intestinal Type<br />
  19. 19. Gastric Cancer – Linitis Plastica<br />Tumor<br />Gastric antrum<br />
  20. 20. Accuracy of Upper GI Series<br />Concern about missing gastric cancer<br />Double-contrast upper GI studies - sensitivity of more than 95% <br />Anatomical shifting of cancer toward the proximal stomach<br />carcinomas of the cardia and fundus now comprise 30% to 40% <br />difficult to evaluate by barium studies<br />
  21. 21. Endoscopy<br />Procedure of choice<br />Sensitivity – 95% for advanced gastric cancer<br />Ability to take biopsies<br />Perform on any patient with dypepsia >45y<br />Perform on any patient with alarm symptoms<br />
  22. 22. Normal Gastroscopy<br />Gastric fundus<br />Gastric body<br />Pylorus<br />Gastric antrum<br />
  23. 23. Gastric Cancer<br />Lauren classification<br />Diffuse type 30 - 40% <br />Younger patients<br />Genetic mutations <br />“Linitis plastica"-type tumour<br />H. pylori not important<br />Intestinal type 60-70%<br />Older age, more men<br />Environmental causes<br />Discrete tumour <br />H.pylori important<br />
  24. 24. Pathology<br />Intestinal Type<br />Diffuse Type<br />
  25. 25. Signet Ring Cells<br />
  26. 26. CT<br />65% to 90% sensitivity for advanced gastric cancer<br />50% for early gastric cancers<br />CT has trouble discerning metastases less than 5 mm in size<br />CT is mainly for the detection of distant metastases and as a complement to EUS for assessing regional lymph node involvement<br />
  27. 27. Endoscopic UltrasoundStaging<br />Early vs advanced - 90% to 99% accurate<br />EUS is comparable to CT detecting perigastric nodes<br />accuracy ranging around 50% to 80%<br />
  28. 28. Clinical Stage-TNM System<br /> Tis: Carcinoma in situ: intraepithelial tumor without invasion of the lamina propriaT1: Tumor invades lamina propria or submucosaT2: Tumor invades the muscularis propria or the subserosaT3: Tumor penetrates the serosa (visceral peritoneum) without invading adjacent structuresT4: Tumor invades adjacent structures<br />
  29. 29. Staging: Nodes and Metastases (TNM)<br />Regional Lymph Nodes (N)<br />N0: No regional lymph node metastasis <br />N1: Metastasis in 1 to 6 regional lymph nodes <br />N2: Metastasis in 7 to 15 regional lymph nodes <br />N3: Metastasis in more than 15 regional lymph nodes<br />Distant metastasis (M)<br />MX: Distant metastasis cannot be assessed<br />M0: No distant metastasis<br />M1: Distant metastasis <br />
  30. 30. Treatment<br />Surgery – only hope of cure<br />Chemotherapy<br />Radiotherapy<br />
  31. 31. Gastric Cancer - Prognosis<br />1-5-year relative survival rates for gastrectomy patients<br />
  32. 32. Lymphoma<br />Malignancies of the lymphatic system<br />Hodgkin’s and Non-Hodgkin’s lymphoma (NHL)<br />GI lymphomas (Ly) are almost always NHL<br />GI tract may be involved as part of the general involvement or the only site (secondary or primary)<br />May be B cell (85%) or T-cell (15%)<br />
  33. 33. Gastric Lymphoma<br />Stomach can be the primary site <br />The stomach can be secondarily involved in disseminated nodal disease <br />20% of all gastric tumors<br />90% are B-cell Lymphomas<br />40% low grade mucosa-associated lymphoid tissue or MALT<br />50% diffuse large B-cell lymphoma<br />
  34. 34. Maltoma<br />Normal gastric tissue does not have lymphoid tissue<br />Chronic antigenic stimulation by H pylori may be the initiating event in the pathogenesis of gastric MALT lymphoma<br />H.pylori infection causes gastritis which leads to lymphoid aggregates, lymphoid hyperplasia, clonal expansion <br />
  35. 35. Clinical<br />Epigastric pain<br />Dypepsia<br />
  36. 36. Maltoma<br />
  37. 37. Low Grade MALToma Treatment<br />Early stage low grade and Helicobacter pylori positive – 95% of maltomas –eradication<br />60-80% respond<br />Complete regression may take >12 m<br />Endoscopic and EUS follow-up required<br />Advanced - chemotherapy<br />
  38. 38. Diffuse Large B-cell LymphomaClinical<br />Pain<br />Nausea<br />Vomiting<br />Anorexia, weight loss<br />Fever<br />Night sweats<br />Diarrhea<br />
  39. 39. Lymphoma - Upper GI series<br />Tumor<br />
  40. 40. Lymphoma - Gastroscopy<br />Gastric Lymphoma<br />Maltoma<br />
  41. 41. CT - Gastric Lymphoma<br />Low Grade Malt Lymphoma<br />High Grade Malt Lymphoma<br />
  42. 42. Diffuse Large B-cell Lymphoma Treatment <br />Chemotherapy<br />Radiotherapy<br />Surgery<br />
  43. 43. Carcinoid<br />Neuroendocrine tumors<br />Enterochromaffin cells (EC) of the gastrointestinal tract<br />Stain with potassium chromate (chromaffin), a feature of cells that contain serotonin<br />The clinical characteristics of carcinoid tumors vary with the location of the tumor <br />
  44. 44. Carcinoids of the GI Tract<br />Carcinoid malignancies originating from 3 areas: <br />Foregut<br />esophagus, stomach and the bronchial tree of the lungs; <br />Midgut<br />pancreas, duodenum, ilium and appendix; and <br />Hindgut<br />ascending, descending and transverse colons and rectum<br />
  45. 45. Gastric Carcinoid - Types<br />Type 1 - Hypergastrinemia <br />Pernicious anemia and chronic atrophic gastritis<br />usually multiple, small and benign, <br />Type 2 - Hypergastrinemia<br />multiple endocrine neoplasia type 1 (MEN1) combined with Zollinger-Ellison syndrome<br />Small, multiple and can metastasize<br />Type 3 No hypergastrinaemia<br />Highly malignant and metastasize<br />
  46. 46. Hypergastrinemia<br />Gastrin Causes ECL Hyperplasia<br />
  47. 47. Carcinoid<br />Average at diagnosis – 62y<br />Male = Female<br />Usually asymptomatic – incidental finding at gastroscopy<br />EUS helps define invasion<br />Biopsies stain for chromogranin<br />
  48. 48. Treatment <br />Type 1<br />Spontaneous resolution <br />Endoscopic polypectomy <br />Antrectomy <br />Total gastrectomy<br />Hydrochloric acid<br />Type 2/3<br />Surgery<br />
  49. 49. Gastric Carcinoid - Prognosis<br />