Upper Gastrointestinal Cancers Niraj Jani, MD


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Upper Gastrointestinal Cancers Niraj Jani, MD

  1. 1. Upper Gastrointestinal Cancers Niraj Jani, MD Division of Gastroenterology Sinai Hospital
  2. 2. Question 1 <ul><li>56 yo WM presents with new onset solid food dysphagia and weight loss. He smokes 1 PPD, weekly alcohol intake and uses antacids frequently. As his internist, you should first: </li></ul><ul><ul><ul><li>Order a barium esophagram </li></ul></ul></ul><ul><ul><ul><li>Refer to a gastroenterologist </li></ul></ul></ul><ul><ul><ul><li>Order a CT scan </li></ul></ul></ul><ul><ul><ul><li>Prescribe a PPI and f/u in 6 weeks </li></ul></ul></ul>
  3. 3. Question 2 <ul><li>The patient’s symptoms in Q1 are most likely NOT secondary to: </li></ul><ul><ul><ul><li>GERD </li></ul></ul></ul><ul><ul><ul><li>Adenocarcinoma of the esophagus </li></ul></ul></ul><ul><ul><ul><li>Squamous Cell Cancer of the esophagus </li></ul></ul></ul><ul><ul><ul><li>Zenker’s diverticulum </li></ul></ul></ul>
  4. 4. Esophageal Cancer <ul><li>Two types: </li></ul><ul><ul><ul><li>Squamous Cell Carcinoma (SCC) - previously the most dominant esophageal cancer and worldwide accounts for 30-40% of esophageal ca </li></ul></ul></ul><ul><ul><ul><li>Adenocarcinoma - over past two decades incidence is rising. Incidence within Barrett’s is 0.4-0.5%/yr </li></ul></ul></ul><ul><ul><ul><li>Now both tumors occur with equal frequency </li></ul></ul></ul><ul><ul><ul><li>Differ in tumor location, predisposing factors, prognosis and treatment </li></ul></ul></ul>
  5. 5. Pathogenesis <ul><li>SCC - mutations in the cyclin D1 gene which is involved in cell cycling and cyclin-dependent kinases </li></ul><ul><li>This complex phosphorylates the retinoblastoma gene (Rb) which leads to increased cell cycling </li></ul><ul><li>Other abnormalities include mutations in the B-catenin/E-cadherin gene and activation of tumor angiogenesis factors (VEGF/EGF) </li></ul>
  6. 6. Pathogenesis <ul><li>Adenocarcinoma - inactivation of the p16 gene through hypermethylation of its promoter </li></ul><ul><li>This leads to increased cell cycling, genetic instability and formation of p53 mutations, aneuploidy </li></ul>
  7. 7. Risk Factors <ul><li>Epidemiology of esophageal cancer in the United States </li></ul><ul><li> Squamous cell Adenocarcinoma </li></ul><ul><li>New cases per year 6000 6000 </li></ul><ul><li>Male-to-female ratio 3:1 7:1 </li></ul><ul><li>Black-to-white ratio 6:1 1:4 </li></ul><ul><li>Most common location Middle esophagus Distal esophagus </li></ul><ul><li>Major risk factors Smoking, alcohol Barrett's esophagus </li></ul>
  8. 8. Esophageal Cancer and BE <ul><li>Incidence of Adenocarcinoma of esophagus is increasing- 3.2/100,000 people from 0.7/100,000 in the 1970’s </li></ul><ul><li>Overall risk of adenoca in BE is 30-52 times higher than general population, however most people with BE will never develop dysplasia or cancer </li></ul>
  9. 9. Trends in Age-adjusted Incidence Rates of Adenocarcinoma Rates per 100,000
  10. 10. Clinical Presentation <ul><li>Dysphagia occurs in 90% of patients, odynophagia 50% </li></ul><ul><li>Solids more problematic than liquids </li></ul><ul><li>Other symptoms may include hoarseness, hematemesis, and nausea </li></ul><ul><li>More advanced disease may cause feeling of “food getting stuck” or regurgitation </li></ul><ul><li>Weight loss common </li></ul>
  11. 11. Diagnosis/Staging <ul><li>Barium Esophagram- more accurate with larger lesions- may serve as initial test to w/u dysphagia </li></ul><ul><li>Endoscopy with biopsies </li></ul><ul><li>Endoscopic Ultrasound </li></ul><ul><li>CT/PET </li></ul>
  12. 12. Diagnosis/Staging
  13. 13. Histology Squamous Cell Cancer Adenocarcinoma
  14. 14. EUS-Esophageal Cancer
  15. 15. EUS-Esophageal Cancer
  16. 16. Diagnosis/Staging <ul><li>EUS - Sensitivity for T staging is 90%, N (lymph node) staging is 80% </li></ul><ul><li>Limitations: cannot detect distant disease and overstages T3 lesions </li></ul><ul><li>CT - T staging sensitivity 60%. Useful for detecting distant disease and T4 lesions </li></ul>
  17. 17. Diagnosis/Staging <ul><li>PET - used with CT to create a fusion image that allows the CT image to be correlated with the nuclear scan </li></ul><ul><li>Valuable in detecting nodal mets and detecting residual cancer after treatment </li></ul><ul><li>Poor at T staging and for lesions less than 1 cm </li></ul>
  18. 18. PET Scan –Esophageal Ca
  19. 19. Treatment <ul><li>Chemotherapy - cisplatin based results in 42-64% response rate. Combination therapy for advanced disease </li></ul><ul><li>Other agents include fluorouracil, taxanes, irinotecan </li></ul><ul><li>Radiotherapy - used in combination with chemo- main benefit is relieving dysphagia by shrinking tumor </li></ul>
  20. 20. Treatment <ul><li>Endoscopic Therapy - T1 lesions - Photodynamic therapy or EMR </li></ul><ul><li>Surgery - esophagectomy (Ivor-Lewis) is primary treatment </li></ul><ul><li>Overall mortality rate from procedure is 5-10%, morbidity 10% from anastomotic leakage, pulmonary problems, cardiac events </li></ul><ul><li>Survival rate- 20% at 1 yr, 5% at 5 years </li></ul>
  21. 21. Treatment <ul><li>Most beneficial in Stage I, II disease </li></ul><ul><li>Debate is whether pre-operative neoadjuvant therapy affects outcome </li></ul><ul><li>Resectable lesions- improves survival 7-9% at 2 years </li></ul><ul><li>Goal is to make pt node negative </li></ul><ul><li>Main Problem- 50-60% present with incurable locally advanced or metastatic disease </li></ul>
  22. 22. Question 3 <ul><li>The most common malignancy of the stomach is: </li></ul><ul><ul><ul><li>A. Lymphoma </li></ul></ul></ul><ul><ul><ul><li>B. Carcinoid tumor </li></ul></ul></ul><ul><ul><ul><li>C. Adenocarcinoma </li></ul></ul></ul><ul><ul><ul><li>D. MALToma </li></ul></ul></ul><ul><ul><ul><li>E. GIST </li></ul></ul></ul>
  23. 23. Question 4 <ul><li>Primary treatment of a MALT lymphoma of the stomach is: </li></ul><ul><ul><ul><li>Surgical resection </li></ul></ul></ul><ul><ul><ul><li>Endoscopic Mucosal Resection (EMR) </li></ul></ul></ul><ul><ul><ul><li>Chemotherapy </li></ul></ul></ul><ul><ul><ul><li>Radiation </li></ul></ul></ul><ul><ul><ul><li>Eradication of H. Pylori </li></ul></ul></ul>
  24. 24. Gastric Cancer <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><ul><li>Risk Factors : Diet, Genetics, H. Pylori infection, Pernicious anemia, Pts with partial gastrectomy, Atrophic gastritis, Menetrier’s disease </li></ul>
  25. 25. Risk Factors <ul><li>Dietary Factors- foods rich in nitrates, nitrites, preserved meat and vegetables </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>
  26. 26. 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>
  27. 27. 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>
  28. 28. Gastric Cancer
  29. 29. 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><ul><ul><li>Sister Mary Joseph’s node </li></ul></ul></ul><ul><ul><ul><li>Virchow’s node </li></ul></ul></ul>
  30. 30. Diagnostic Studies <ul><li>Contrast radiograpy - may be initial test for vague symptoms </li></ul><ul><li>Endoscopy </li></ul><ul><li>CT - cannot determine depth of invasion. Good for detecting distant disease </li></ul><ul><li>EUS - more accurate and T and N staging than CT </li></ul>
  31. 31. 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>
  32. 32. Treatment <ul><li>Surgical resection and lymph node removal are the only chance for cure </li></ul><ul><li>66% of patients present with advanced disease that is 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>
  33. 33. Gastric Cancer <ul><li>Gastric Lymphoma - most 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>
  34. 34. 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>
  35. 35. Other Gastric Tumors <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><ul><li>GIST - originate usually from the muscularis propria- need to differentiate from leiomyoma, leiomyosarcoma, lipoma </li></ul>
  36. 36. Other Gastric Lesions
  37. 37. EUS-Stomach
  38. 38. Small Bowel Cancers <ul><li>Adenocarcinoma- know about FAP, HNPCC </li></ul><ul><li>Lymphomas- especially in AIDS pt </li></ul><ul><li>Crohn’s disease </li></ul><ul><li>Celiac disease </li></ul><ul><li>Neuroendocrine tumors </li></ul><ul><li>Gardner’s, Peutz-Jegher’s, Juvenile Polyposis syndrome, Cowden disease </li></ul>