Gastric Cancer 09.


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Gastric cancer: 2009 update.

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Gastric Cancer 09.

  1. 1. Gastric tumors: <ul><li>Benign : </li></ul><ul><li>Polyps </li></ul><ul><li>Lieomyoma (Gastrointestinal stromal tumor GIST ) </li></ul><ul><li>Malignant : </li></ul><ul><li>Adenocarcinoma 85% </li></ul><ul><li>Lymphoma 5% </li></ul><ul><li>GIST Sarcoma </li></ul><ul><li>Carcinoid </li></ul><ul><li>Others </li></ul>
  2. 3. Gastric polyps: <ul><li>Hyperplastic – </li></ul><ul><li>Benign, inflammatory,hamartomas 75% </li></ul><ul><li>Adenomatous – </li></ul><ul><li>Premalignant </li></ul><ul><li>Mixed </li></ul><ul><li>Part of FAP syndrome </li></ul>
  3. 4. Gastric Cancer <ul><li>Gastric cancer </li></ul><ul><ul><li>Adenocarcinoma </li></ul></ul><ul><ul><li>GIST (gastro-intestinal stromal tumour) </li></ul></ul><ul><ul><li>Carcinoid </li></ul></ul><ul><ul><li>Lymphoma </li></ul></ul><ul><ul><li>other </li></ul></ul>
  4. 5. Pathohistologic classification <ul><li>Histology </li></ul><ul><li>Adenocarcinoma 90% </li></ul><ul><li>Lymphoma 5% </li></ul><ul><li>GI Stromal tumor 2% </li></ul><ul><li>Carcinoid <1% </li></ul><ul><li>Metastasis <1% </li></ul><ul><li>Adenosquamous/squamous <1% </li></ul><ul><li>Miscellaneous <1% </li></ul>
  5. 6. Adenocarcinoma – Lauren classification <ul><li>Diffuse </li></ul><ul><ul><li>Linitis plastica type </li></ul></ul><ul><ul><li>Poorer prognosis </li></ul></ul><ul><li>Intestinal </li></ul><ul><ul><li>Localised </li></ul></ul><ul><ul><li>Better prognosis </li></ul></ul><ul><ul><li>Distal stomach </li></ul></ul>
  6. 7. Gastric Cancer: Adenocarcinoma <ul><li>750,000 cases annually. 22,000 new cases in the US each year </li></ul><ul><li>Rise in cancer of the proximal stomach and GEJ </li></ul>
  7. 8. Risk Factors <ul><li>Diet </li></ul><ul><li>Genetics </li></ul><ul><li>H. Pylori infection: very important cause. </li></ul><ul><li>Pernicious anemia </li></ul><ul><li>Pts with partial gastrectomy </li></ul><ul><li>Vagotomy. </li></ul><ul><li>Atrophic gastritis </li></ul><ul><li>Menetrier’s disease </li></ul>
  8. 9. Risk Factors <ul><li>Dietary Factors- foods rich in nitrates, nitrites, preserved meat & vegetables(smoked/salted). </li></ul><ul><li>Genetic Factors - Lynch syndrome II. Microsatellite instability (MSI) is present in up to 33% of gastric cancers </li></ul><ul><li>Pernicious Anemia - auto-immune atrophic gastritis increased risk by 2-3x </li></ul>
  9. 10. Risk Factors <ul><li>Partial gastrectomy- slightly increased risk </li></ul><ul><li>Menetrier’s Disease - rugal fold hypertrophy, hypochlorhydria and protein-losing enteropathy </li></ul><ul><li>Adenomatous Gastric Polyps </li></ul>
  10. 11. Gastric Cancer Environmental factors H. pylori Genetic factors Etiological Factors of Gastric Cancer Precancerous changes
  11. 12. Pathologic Features <ul><li>Distal cancer- H. Pylori related </li></ul><ul><li>Proximal cancer- GERD/Barrett’s dz </li></ul><ul><li>Chronic gastritis  Atrophic Gastritis  Intestinal Metaplasia  Dysplasia/Cancer </li></ul><ul><li>Intestinal type vs diffuse type </li></ul>
  12. 13. Gastric Cancer
  13. 14. Clinical Features <ul><li>Vague symptoms- early satiety, abdominal pain, bloating, dyspepsia, wt loss, anorexia </li></ul><ul><li>GI bleeding, microcytic anemia, vomiting if GOO present </li></ul><ul><li>Associated paraneoplastic syndromes- </li></ul><ul><ul><ul><li>Acanthosis Nigricans </li></ul></ul></ul><ul><ul><ul><li>Venous Thrombi (Trousseau’s syndrome) </li></ul></ul></ul><ul><li>Metastasis: </li></ul><ul><ul><ul><li>Sister Mary Joseph’s node </li></ul></ul></ul><ul><ul><ul><li>Virchow’s node </li></ul></ul></ul><ul><ul><ul><li>Liver secondaries. </li></ul></ul></ul>
  14. 15. Clinical manifestation <ul><li>Signs/Symptoms of Early Gastric Cancer </li></ul><ul><li>Asymptomatic or silent 80% </li></ul><ul><li>Peptic ulcer symptoms 10% </li></ul><ul><li>Nausea or vomiting 8% </li></ul><ul><li>Anorexia 8% </li></ul><ul><li>Early satiety 5% </li></ul><ul><li>Abdominal pain 2% </li></ul><ul><li>Gastrointestinal blood loss <2% </li></ul><ul><li>Weight loss <2% </li></ul><ul><li>Dysphagia <1% </li></ul>
  15. 16. Signs and Symptoms <ul><li>Advanced Gastric Cancer </li></ul><ul><li>Weight loss 60% </li></ul><ul><li>Abdominal pain 50% </li></ul><ul><li>Nausea or vomiting 30% </li></ul><ul><li>Anorexia 30% </li></ul><ul><li>Dysphagia 25% </li></ul><ul><li>Gastrointestinal blood loss 20% </li></ul><ul><li>Early satiety 20% </li></ul><ul><li>Peptic ulcer symptoms 20% </li></ul><ul><li>Abdominal mass or fullness 5% </li></ul><ul><li>Asymptomatic or silent <5% </li></ul>Duration of symptoms Less than 3 month 40% 3-12 months 40% Longer than 12 month 20%
  16. 17. Special signs & terms <ul><li>Linitis plastica: diffusely infiltrating with a rigid stomach </li></ul><ul><li>Virchow’s node: supraclavicular lymphadenopathy (left) </li></ul><ul><li>Irish’s node: axillary lymphadenopathy </li></ul><ul><li>Sister Mary Joseph’s node: umbilical lymphadenopathy </li></ul>
  17. 18. Laboratory tests Iron deficiency anemia Fecal occult blood test (FOBT) Tumor markers (CEA, Ca19-9)
  18. 19. Diagnostic Studies <ul><li>Contrast radiograpy( Barium) - may be initial test for vague symptoms. </li></ul><ul><li>Endoscopy: the usual diagnostic method with the use of image enhancing methods as chromo endoscopy for early detection of small lesions. </li></ul><ul><li>CT - cannot determine depth of invasion. Good for detecting distant disease </li></ul><ul><li>EUS - more accurate for T / N staging than CT </li></ul>
  19. 20. Staging/Prognosis <ul><li>Early gastric cancer- 5-yr survival rate of 80-90% </li></ul><ul><li>Survival for Stage III or IV disease is 5-20% at 5 years </li></ul>
  20. 21. T stage (UICC TNM 2002) T1 T3 T2b T2a T1 Adjacent structure T4
  21. 22. N & M stage (UICC TNM 2002) <ul><li>N stage </li></ul><ul><ul><li>N0 - no nodes </li></ul></ul><ul><ul><li>N1 - 1-6 nodes </li></ul></ul><ul><ul><li>N2 - 7-15 nodes </li></ul></ul><ul><ul><li>N3 > 15 nodes </li></ul></ul><ul><li>M stage </li></ul><ul><ul><li>M0 – no distant metastases </li></ul></ul><ul><ul><li>M1 – distant metastases (includes distant nodes </li></ul></ul>
  22. 24. Early GC: <ul><ul><li>Incidence of EGC increased from 1-15% </li></ul></ul><ul><ul><ul><li>Due to Open access endoscopy </li></ul></ul></ul><ul><li>For early diagnosis urgent (<2 weeks) specialist referral for endoscopic investigation indicated when dyspepsia with: </li></ul><ul><ul><li>Chronic GI bleeding </li></ul></ul><ul><ul><li>Progressive unintentional wt loss </li></ul></ul><ul><ul><li>Progressive dysphagia </li></ul></ul><ul><ul><li>Persistent vomiting </li></ul></ul><ul><ul><li>Iron deficiency anaemia </li></ul></ul><ul><ul><li>Epigastric mass </li></ul></ul><ul><ul><li>Suspicious barium meal </li></ul></ul>
  23. 25. Early GC: <ul><li>Mostly Japanese. </li></ul><ul><li>Confined to the mucosa &submucosa, irrespective of nodal state, </li></ul><ul><li>Surgical resection may be curative &definitely improves the 5-year survival rate to > 50%. </li></ul><ul><li>When early gastric cancer is confined to the mucosa, endoscopic mucosal resection (EMR) may be an alternative. </li></ul>
  24. 26. Treatment <ul><li>The only chance for cure is surgical resection, possible in 25-30%. </li></ul><ul><li>If confined to the distal stomach, subtotal gastrectomy with resection of lymph nodes in the porta hepatis & pancreatic head. </li></ul><ul><li>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. </li></ul><ul><li>Limited gastric resection is necessary for patients with excessive bleeding or obstruction& If cancer recurs in the gastric remnant. </li></ul><ul><li>66% present with advanced disease incurable by surgery alone </li></ul><ul><li>Resistant to radiotherapy- used mostly for palliation </li></ul><ul><li>Chemo- decreases tumor burden in 15% of patients at best </li></ul>
  25. 27. Gastric lymphoma: <ul><li>M ost of B-cell origin </li></ul><ul><li>Primary gastric lymphoma rare </li></ul><ul><li>Non-Hodgkin’s most common type </li></ul><ul><li>5 year survival rate is 50% </li></ul>
  26. 28. Gastric lymphoma: <ul><li>5% of all malignant gastric tumors. </li></ul><ul><li>Increasing in incidence. </li></ul><ul><li>The majority are non-Hodgkin’s lymphomas & the stomach is the most common extranodal site for non-Hodgkin’s lymphomas. </li></ul><ul><li>Generally younger than those with gastric adenocarcinoma,also male predominance. </li></ul><ul><li>Commonly present with symptoms & signs similar to adenoca. </li></ul><ul><li>Lymphoma in the stomach can be a primary tumor or can be due to disseminated lymphoma. </li></ul><ul><li>B-cell lymphomas of the stomach are most commonly large cell with a high-grade type. </li></ul><ul><li>Low-grade variants are noted in the setting of chronic gastritis called mucosa-associated lymphoid tissue (MALT) lymphomas. strongly associated with H. pylori infection. </li></ul>
  27. 29. Gastric lymphoma: diagnosis <ul><li>Ba: usually ulcers or exophytic masses; a diffusely infiltrating lymphoma is more suggestive of secondary lymphoma. </li></ul><ul><li>Primary gastric lymphoma, Barium usually show multiple nodules& ulcers. </li></ul><ul><li>Secondary lymphoma typically have the appearance of linitis plastica. </li></ul><ul><li>UGI endoscopy with biopsy/cytology are required for diagnosis with accuracy of 90%. </li></ul><ul><li>Conventional histopathology& immunoperoxidase staining for lymphocyte markers is helpful in diagnosis. </li></ul><ul><li>Proper staging of gastric lymphoma involves EUS, chest& abdominal CT scans& bone marrow biopsy. </li></ul>
  28. 30. Gastric lymphoma: Treatment <ul><li>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%. </li></ul><ul><li>For MALT lesions, eradication of H. pylori with antibiotics induces regression of the tumor, but longer term follow-up is needed. </li></ul><ul><li>Radiotherapy can be curative for localized MALT lymphomas. </li></ul>
  29. 31. MALTomas <ul><li>Low grade B-cell lymphoma associated with chronic H. Pylori infection </li></ul><ul><li>EUS is most reliable method for staging </li></ul><ul><li>Treatment of H. Pylori eradicates the tumor </li></ul>
  30. 32. Other Gastric Tumors <ul><li>GIST - originate usually from the muscularis propria. </li></ul><ul><li>Carcinoid Tumors - 0.3% of all gastric tumors. Produce 5-HIAA and can cause carcinoid syndrome. May lead to hyper-gastrinemia </li></ul>
  31. 33. GIST: <ul><li>Gastro Intestinal Stromal Tumors </li></ul><ul><li>Around 5,000 to 6,000 new cases each year </li></ul><ul><li>Tends to occur in middle aged persons with a slight male predilection </li></ul><ul><li>Occur throughout the GI tract </li></ul>
  32. 34. GIST: <ul><li>Stomach 50-60% </li></ul><ul><li>Small bowel 20-30% </li></ul><ul><li>Large bowel 10% </li></ul><ul><li>Esophagus 5% </li></ul><ul><li>Else where in abdomen 5% </li></ul><ul><li>Symptoms depend on the site& size of the tumor: </li></ul><ul><ul><li>Abdominal pain </li></ul></ul><ul><ul><li>Dysphagia </li></ul></ul><ul><ul><li>Gastrointestinal bleeding </li></ul></ul><ul><ul><li>Symptoms of bowel obstruction </li></ul></ul><ul><ul><li>Small tumors may be asymptomatic </li></ul></ul><ul><ul><li>Diagnosis: Light microscopy with Immuno-histochemistry </li></ul></ul>
  33. 35. GIST: <ul><li>Features favoring benign lesions in general like: </li></ul><ul><ul><li>Size less than 5 cm </li></ul></ul><ul><ul><li>Low number of mitosis per HPF </li></ul></ul><ul><ul><li>No mucosal invasion </li></ul></ul><ul><ul><li>Low cellularity </li></ul></ul><ul><ul><li>Low markers of cell proliferation </li></ul></ul><ul><li>The above have shown to be associated with malignant behavior in some but not in other studies. </li></ul><ul><li>With prolonged follow up any GIST has the potential to behave in a malignant fashion. </li></ul><ul><li>50% of primary localized tumors that are resected relapse after 5 years of follow up. </li></ul>
  34. 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 <ul><li>>5 cm </li></ul><ul><li>>10 cm </li></ul><ul><li>Any size </li></ul><ul><li>>5/50 HPF </li></ul><ul><li>Any count </li></ul><ul><li>>10/50 HPF </li></ul>
  35. 37. <ul><li>Since activation of Kit played a crucial role in the pathogenesis of GIST, inhibition of Kit would be therapeutic. </li></ul><ul><li>Imatinib was found to be effective in GIST. </li></ul><ul><li>Indicated for large tumors pre or postoperative. </li></ul>
  36. 38. Prognosis: <ul><li>The 5-year survival for malignant GIST varies widely from 28 to 80%. </li></ul><ul><li>Median survival of patients in whom complete surgical resection is not possible is 10–23 months. </li></ul><ul><li>The median survival from the time of diagnosis of metastatic or recurrent disease has been reported from 12 to 19 months. </li></ul>
  37. 39. Gastric carcinoids: <ul><ul><li>Relatively uncommon. </li></ul></ul><ul><ul><li>They are grouped into three categories </li></ul></ul><ul><ul><li>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. </li></ul></ul><ul><ul><li>Type 2 occur in association with gastrinomas (Zollinger-Ellison syndrome) MEN type 1. </li></ul></ul><ul><ul><li>They account for <5% of gastric carcinoids. Similar to carcinoids in atrophic gastritis, the tumors are thought to arise from ECL cells. </li></ul></ul><ul><ul><li>Type 3 known as sporadic carcinoids occur in the absence of atrophic gastritis or ZES or MEN-1 syndromes. </li></ul></ul><ul><ul><li>Account for 20 % of gastric carcinoids, are the most aggressive; local or hepatic metastases are present in up to 65 % who come to resection. </li></ul></ul>
  38. 40. Gastric cancers
  39. 41. Endoscopic features of gastric cancer
  40. 42. EUS-Stomach