Gastric Carcinoma

1. Gastric Carcinoma

2. Background • Second most common cancer-related death. • Korea, Japan, China, Taiwan high rates. • 22,000 diagnosed annually in US. • 14th most common cancer. • Difficult to cure, as advanced disease. • Most die of recurrent disease even after resection for cure.

4. Anatomy • Stomach begins at GE junction, ends at duodenum. • 3 parts- uppermost is cardia, largest part in middle is body, the last part is pylorus. • Cardia contains mucin producing cells. • Fundus or body mucoid cells, chief cells, parietal cells. • Pylorus has mucin producing cells.

5. Anatomy • Five layers: Mucosa, submucosa, muscular layer, subserosal layer, serosal layer. • Peritoneum of greater sac covers anterior surface • A portion of lesser sac drapes posteriorly over stomach. • The GE junction has limited serosal covering.

6. Anatomy • The site of the lesion is classified on basis of relationship to long axis of stomach. • 40% lower part • 40% middle part • 15% upper part • 10% more than one part • Recently the # of lesions proximally has increased.

8. Pathophysiology • Understand vascular supply, allows for understanding of routes of spread. • Derived from celiac artery. • Left gastric supplies upper right stomach. • Right gastric off common hepatic- lower portion. • Right gastroepiploic -lower portion of greater curve.

9. Pathophysiology • Understanding lymphatic drainage can clarify nodal involvement. • Complex drainage • Primarily along celiac axis. • Minor drainage along splenic hilum, suprapancreatic nodal groups, porta hepatis, and gastroduodenal areas

10. Frequency • US: seventh leading cause of cancer deaths, with 22,000 diagnosed yearly, and 14,000 deaths. • Internationally: second most common cancer. Tremendous geographic variation, with highest death rates in Chile, Japan, and former USSR.

11. Mortality and Morbidity • 5-year survival for curative resections ranges from 30-50% for stage II disease and 10-25% in stage III. • High likelihood of systemic and local relapse. • Adjuvant therapy is offered . • Operative mortality is less than 3% for curative resections.

12. Race • Higher in Asian countries. • Japanese detect patients at very early stage, patients appear to do quite well. • In Asian studies, patients with resected stage II and III disease have better outcomes than similar stages in the west. • Some believe this reflects a biologic difference between diseases in Asia and west. • Black race, low socioeconomic class.

13. Sex, Age • Men>women • Most are elderly at diagnosis. Median age 65 years. The ones that present in younger patients may represent a more aggressive variant. • Cigarettes

14. History • Early disease has no symptoms, some patients with incidental complaints get an early diagnosis. • If symptoms, it reflects advanced disease; These may include indigestion, nausea, dysphagia, early satiety, anorexia, weight loss.

15. History • Late complications include: pleural effusions, peritoneal effusions, GOO, GE obstruction, SBO, bleeding, jaundice, cachexia.

16. Physical • All physical signs are late events. • Too late for curative procedures. • Palpable stomach with succussion splash, hepatomegaly, Virchow nodes, sister MJ nodes, Blumer shelf, weight loss, pallor from bleeding and anemia.

17. Etiology • Diet • H. Pylori • Previous stomach surgery • Pernicious anemia • Polyps(rarely a precursor) • Atrophic gastritis • Radiation, genetics

18. Diet • Certain diets are implicated. • Rich in pickled vegetables, salted fish, excessive dietary salt, smoked meats. • A diet that includes fruits and vegetables rich in vitamin C may have a protective effect.

19. Helicobacter • Implicated as precursor of gastric cancer. • H. Pylori associated with atrophic gastritis, and patients with a history of prolonged gastritis have a 6-fold increase in risk. • Particularly true of tumors of antrum, body, and fundus of stomach, but not in cardia.

20. Previous Surgery • Implicated as risk factor, the rational being that previous gastric surgery alters normal pH of stomach. • Retrospective studies show that a small percentage of patients who have a gastric polyp removed have evidence of invasive carcinoma in the polyp. • Polyps may therefore be premalignant.

21. Genetic Factors • Poorly understood • Some familial aggregation exists

22. Laboratory • Assists in determining optimal therapy. • CBC identifies anemia, with may be caused by bleeding, liver dysfunction, or poor nutrition. • 30% have anemia. • Electrolyte panels and LFTs are also essential to better characterize patients clinical state.

23. Imaging Studies • EGD: safe, simple, providing a permanent color photographic record. • Obtains tissue for diagnosis. • UGI: detects large tumors, but only occasionally detects extension into esophagus or duodenum, especially if small or submucosal.

26. Imaging Studies • CXR: done to evaluate for metastases. • CT scan or MRI of chest, abdomen, pelvis: evaluate local disease process, and areas of spread. Some tumors are deemed unresectable based on the testing. • Accurately predicts stage 66-77%. • Poor nodal status prediction.

27. Endoscopic Ultrasound • Endoscopic ultrasound: becoming extremely useful as a staging tool, when CT fails to show T3, T4, or metastatic disease. • Used with neoadjuvant chemo to stratify pts • Can achieve resolution of 0.1 mm. • Cannot reliably distinguish between tumor and fibrosis. • Overall staging accuracy of 75% • Poor for T2 lesions (38%) • Better for T1(80%), T3 (90%)

30. Histology • Adenocarcinoma 95% • Lymphomas 2% • Carcinoids 1% • Adenocathomas 1% • Squamous cell 1%

31. Histology • Adenocarcinoma is classified according to the most unfavorable microscopic element present: tubular, papillary, mucinous, signet-ring cells. • Also identified by gross appearance: ulcerative, polypoid, scirrous, superficial spreading, multicentric, or Barrett ectopic. • Variety of other schemes: Borrmann, Lauren.

32. Borrmann Classification • 5 categories • Type I: polypoid or fungating • Type II: ulcerating lesions with elevated borders • Type III: ulceration with invasion of wall • Type IV: diffuse infiltration • Type V: cannot be classified

33. Lauren System • Epidemic or endemic • The intestinal, expansive epidemic type gastric cancer is associated with atrophic gastritis, retained glandular structure, little invasiveness, sharp margins. It would be a Borrmann I or II.

34. Lauren System • The epidemic or Borrmann I or II carries better prognosis, shows no family history. • The diffuse, infiltrative, endemic, is poorly differentiated, with dangerously deceptive margins, invades large areas of stomach. Younger patients, genetic factors, blood groups, and family history.

35. Staging • Primary tumor Tx- cannot be assessed T0- no evidence Tis- carcinoma in situ, no invasion of lamina T1- invades lamina propria or submucosa T2- invades muscularis or subserosa T3- penetrates serosa, no adjacent structure T4- invades adjacent structures

36. Regional Lymph Nodes NX- cannot be assessed N0- no nodes N1- mets in 1-6 regional nodes N2- mets in 7-15 regional nodes N3- mets in more than 15 regional nodes

37. Distant Metastases • MX- cannot be assessed • M0- no distant metastases • M1-distant metastases

38. Prognostic Features • Depth of invasion through gastric wall, presence or absence of regional lymph node involvement • The greater number of positive nodes, the greater the likelihood of local or systemic failure postoperatively

39. Spread Patterns • Directly, via lymphatics, or hematogenously • Direct extension into omentum, pancreas, diaphragm, transverse colon, and duodenum. • If lesion extends beyond wall to a free peritoneal surface, peritoneal involvement is frequent.

40. Spread Patterns • The visible gross lesion frequently underestimates true extent. • Abundant lymphatic channels in submucosal and subserosal layers allow for easy spread. • The submucosal plexus is prominent in esophagus, the subserosal plexus prominent in duodenum, which allows for proximal and distal spread. • Liver mets common, from hematogenous spread.

42. Laparoscopy • Inspect peritoneal surfaces, liver surface. • Identification of advanced disease avoids non-therapeutic laparotomy in 25%. • Patients with small volume metastases in peritoneum or liver have a life expectancy of 3-9 months, thus rarely benefit from palliative resection.

43. Lymph Node Dissection • AJCC: number rather than location of LN is prognostic. • Extent of dissection controversial. • Nodal involvement indicates poor prognosis, and more aggressive approaches to remove them are taking favor. • Ongoing trials regarding this in Europe. • Critics argue that the apparent benefit associated with extended LND reflects stage migration (each LN is reviewed more carefully).

44. Residual Disease R Status • Tumor status following resection. • Assigned based on pathology of margins. • R0- no residual gross or microscopic disease. • R1- microscopic disease only. • R2- gross residual disease. • Long term survival only in R0 resection.

45. “D” Nomenclature • Describes extent of resection and lymphadenectomy. • D1- removes all nodes within 3cm of tumor. • D2- D1 plus hepatic, splenic, celiac, and left gastric nodes. • D3- D2 plus omentectomy, splenectomy, distal pancreatectomy, clearance of porta hepatis nodes. • Current standards include a D1 dissection only.

46. Type of Surgery • In general most surgeons perform total gastrectomy ( if required for negative margins), esophagogastrectomy for tumors of the cardia and GE junction, and a subtotal gastrectomy for tumors of the distal stomach. • Similar 5 year rates for subtotal vs. total in tumors of distal stomach. • Extensive lymphatics require 5cm margin.

47. Outcome • 5-year survival for a curative resection is 30-50% for stage II disease, 10-25% for stage III disease. • Adjuvant therapy because of high incidence of local and systemic failure. • A recent Intergroup 0116 randomized study offers evidence of a survival benefit associated with postoperative chemoradiotherapy

48. Complications • Mortality 1-2% • Anastamotic leak, bleeding, ileus, transit failure, cholecystitis, pancreatitis, pulmonary infections, and thromboembolism. • Late complications include dumping syndrome, vitamin B-12 deficiency, reflux esophagitis, osteoporosis.

49. Adjuvant Therapy • Rationale is to provide additional loco-regional control. • Radiotherapy- studies show improved survival, lower rates of local recurrence when compared to surgery alone. • In unresectable patients, higher 4 year survival with mutimodal tx, in comparison to chemo alone.

50. Chemotherapy • Numerous randomized clinical trials comparing combination chemotherapy in the adjuvant setting to surgery alone did not demonstrate a consistent survival benefit. • The most widely used regimen is 5-FU, doxorubicin, and mitomycin-c. The addition of leukovorin did not increase response rates.