1. Gastric Cancer Matt White AM Report April 19, 2010

2. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

3. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

4. Epidemiology Incidence: 21,260 cases in 2007 – ~7 per 100,000 11,210 cancer deaths in 2007 Mortality significantly decreased in past 75 years (unknown reasons)

5. Gastric tumors 85% adenoocarcinomas 15% lymphomas and gastrointestinal stromal tumors (GIST)

6. Adenocarcinoma Cancer types “Intestinal type” (more common) – Morphologically similar to intestinal adenocarcinomas. Diffuse-type – Lack of intercellular adhesions (germline mutation in protein E-cadherin)

7. Spectrum of gastric cancer Proposed progression: chronic gastritis --> – chronic atrophic gastritis --> intestinal metaplasia --> – dysplasia --> adenocarcinoma

8. Risk Factors for gastric cancer Diet – nitroso compounds – low fruit/vegetable, high fried foods/processed meat – High salt intake Obesity Smoking (HR 2-3) ? Alcohol H. Pylori Low socioeconomic status Hereditary diffuse gastric cancer – 40-67% lifetime risk for men, 60-83% for women Immigrants from endemic areas – maintain native country risk, risk to offspring similar to new homeland

9. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

10. Presentation Approximately 50% of cases present with symptoms and have disease extending beyond locoregional confines Of locoregional cases, only ½ can undergo a potentially curative resection

11. Symptoms at presentation

12. Symptoms (cont’d) Dysphagia: more common with proximal gastric tumors Occult GI bleeding very common, overt bleeding <20%.

13. Less Common Symptoms Pseudoachalasia: if Auerbach’s plexus involved Colonic obstruction: if cancer spreads (direct extension) to colonic wall

14. Signs Palpable abdominal mass: most common physical finding If cancer spreads via lymphatics… – Left supraclavicular node (Virchow’s) – Periumbilical node (Sister Mary Joseph) – Left axillary node (Irish) – Enlarged ovary (Krukenberg's tumor) – Ascites

15. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

16. Diagnosis EGD – Gold standard – Single biopsy from ulcer -> sensitivity ~ 70% – Seven biopsies from ulcer -> sensitivity >98% – Brush cytology increases sensitivity of single biopsies, aid in multiple biopsies unclear

17. Barium studies False negative in as many as 50% of cases Sensitivity as low as 14% in early cases May be superior to EGD for linitis plastica – EGD may be normal while “leather-bottle” will be apparent on radiograph

18. Linitis Plastica Diffuse-type gastric cancer Tumor often infiltrates the submucosa and muscularis propria Superficial biopsies may be falsely negative Combination of strip and bite biopsy needed if suspicious for linitis plastica

19. Linitis Plastica, “leather bottle stomach”

20. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

21. Staging of Gastric Cancer Two systems: – Japanese classification (more elaborate and anatomic based) – Western: developed by American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) -- more widely used Tumors at GE junction of in cardia of stomach within 5cm of GE junction – Classified using esophageal staging

22. Other caveats T stage: dependent on depth of tumor invasion NOT size of lesion Nodal stage: based on # of positive LN rather than location of LNs (proximity to tumor)

23. Staging workup Biopsy Imaging – CT: evaluates for metastases (M stage) 20-30% with negative CT have intraperitoneal disease at laparatomy Accuracy of 50-70% for T stage Slightly worse accuracy for N stage compared to EUS – EUS: most reliable nonsurgical method to evaluate depth of invasion More accurate than CT for T stage 65-90% accurate for N stage

24. Staging workup PET – More sensitive than CT for detection of distant metastases. – Also useful for detecting LNs – Negative PET not helpful- even large tumors can be falsely negative if metabolic activity low. Most diffuse gastric cancers (signet ring) are not FDG avid

25. Staging workup Serologic markers – CEA, CA-125, CA 19-9, CA 72-4 may be elevated but have low sensitivity/specificity – None are diagnostic – Preoperative elevation in markers usually pretends high risk of adverse outcome – No serologic finding should exclude surgical consideration

26. AJCC Staging System

28. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

29. Treatment Locoregional (stage I-III) disease – Potentially curable – Refer for multidisciplinary evaluation and consideration of surgery Advanced (stage IV) disease – Palliative therapy – Studies indicate longer survival and better quality of life with systemic treatment

30. Treatment Complete surgical resection with removal of LNs (only chance of cure) – Possible in < 1/3 of cases Subtotal gastrectomy for distal carcinomas, total or near-total for proximal masses Reduction of tumor bulk (palliative) – Chemotherapy (cisplatin + 5-FU or irinotecan) Partial response in 30-50% of patients – Radiation (for pain control, no mortality benefit with XRT alone)

31. Data from SEER. Patients diagnosed from 1991-2000 (n=14,097). Stage IA (n=1194), stage IB (n=655), stage IIA (n=1161) stage IIB (n=1195), stage IIIA (n=1031), stage IIIB (n=1660), stage IIIC (n=1053), stage IV (n=6148).

32. Prognosis StageTNMFeatures % of Cases* % 5-year survival* 0 TisN0M0Node negative; limited to mucosa 190 IA T1N0M0 Node negative; invasion of lamina propria or submucosa 759 IB T2N0M0 Node negative; invasion of muscularis propria 1044 II T1N2M0 Node positive; invasion beyond mucosa but within wall 1729 T2N1M0 T3N0M0Node negative; extension through wall IIIA T2N2M0 Node positive; invasion of muscularis propria or through wall 2115 T3N1-2M0 IIIB T4N0-1M0 Node negative; adherence to surrounding tissue 149 IV T4N2M0 Node negative; adherence to surrounding tissue 303 Any M1Distant Metastases ** Data from American Cancer Society

33. Objectives Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening/Follow-up

34. Screening Currently screening programs in Japan, Venezuela, Chile due to high incidence – Mostly barium studies, EGD is concerning findings – Some use serum pepsinogen testing for high risk with EGD confirmation – H. pylori: sensitivity 88%, specificity 41% (Japan) – Japan study: 5-year survival 74-80 in screened group, 46- 56% for non-screened group. Not cost effective in US due to relatively low incidence (<10 per 100,000) – Preventing incidence of 1 gastric cancer death estimated to cost $247,600

35. Gastric Ulcers 25% of patient with gastric cancer have history of a gastric ulcer American Society of Gastrointestinal Endoscopy recommendations: – Follow-up EGD in 8-12 weeks to verify healing. – Non-healing ulcers need repeat biopsies Question of cost-effectiveness of repeat endoscopies; however, small (curable) lesions may be missed without follow-up.

36. Take Home Points Most cases present in advanced stage Staging workup (CT vs PET vs EUS) to evaluate extent of disease Staging laparoscopy indicated for medically fit patients with >T1 lesion and without stage IV disease Ensure follow-up of ulcers seen on EGD No effective screening in US patients

37. References Harrison’s Principles of Internal Medicine Up to Date