CARCINOMA STOMACH etiopathogenesis..pptx

Stomach Ca.

1. dr. mayank raj karn Resident 2 nd year ( general surgery) 1 CARCINOMA STOMACH (ETIOPATHOGENESIS, CLINICAL FEATURES, DIAGNOSIS)

2. CONTENT Introduction Risk factors Pathology Clinical features Diagnosis and staging 2

3. INTRODUCTION Fifth most common cancer and the second leading cause of cancer death. M ajor cause of mortality worldwide . A n eminently curable disease and early diagnosis is key to success . Male >> Female; older individuals, peak incidence in the seventh decade. The most common primary malignant gastric neoplasm A denocarcinoma (95 %); Lymphoma and GIST 3

4. ETIOPATHOGENESIS Protective and risk factors for stomach carcinoma Protective Antioxidant Vit A, C Selenium, Zinc, Iron Citrus Fruits Raw vegetables Green tea 4

5. Genetic risk factors Pernicious anemia Family history HNPCC Peutz-Jeghers syndrome FAP Type A blood Li- Fraumeni Acquired Risk factors H. Pylori EBV Previous stomach surgery Smoked / cured food High salt /Nitrate diet smoking Coal workers Rubber workers Contaminated well water Radiation exposure Precursors Adenoma Intestinal metaplasia Atropic gastritis Menetrier disease Dysplasia 5

6. ETIOPATHOGENESIS Risk Factors Helicobacter pylori Infection Most common cause of infection-related cancers. H. pylori seropositivity – approximately sixfold increased risk of developing gastric cancer . 6

7. Primary mechanism -- the presence of chronic inflammation. Long term infection -- atrophic gastritis or chronic active gastritis (primarily in the body-ventral gastric atrophy). G astritis progresses to intestinal metaplasia, dysplasia, and ultimately intestinal-type adenocarcinoma. 7

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9. H. Pylori – molecular alterations in intestinal metaplasia O verexpression of cyclooxygenase-2 and cyclin D2. p53 mutations. M icrosatellite instability. D ecreased p2 7 expression . A lterations in transcription factors such as CDX1 and CDX2 . Individual with high levels of interleukin-1β and tumor necrosis factor-α expression– High risk. Presence of cytotoxin -associated gene A ( CagA ) – high chance of Ca. 9

10. Dietary factors Salted / Smoked food – contains High levels of Nitrates – converted to N- nitoso compounds by bacteria in the stomach. N- nitroso compounds found in Tobacco smoke . Fresh fruits and vegetables – contains Ascorbic acid – remove N- niroso compounds and oxygen free radicals. 10

11. H. Pylori and Diet Synergism. Increasing carcinogen production and inhibiting its removal . Promote the growth of the bacteria that generate the carcinogenic N- nitroso compounds. I nhibit the secretion of ascorbic acid 11

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13. Hereditary Risk Factors Hereditary diffuse gastric cancer Mutation for the cell adhesion molecule E-cadherin (CDH1 ) have 60% to 70% lifetime incidence of developing gastric cancer . Prophylactic total gastrectomy -- prior to age 30 . These patients are also at higher risk of lobular breast cancer and screening should begin by age 30. 13

14. Familial adenomatous polyposis Fundic gland polyp seen in 85% cases. 40% of these having Dysplasia. >50% contain somatic adenomatosis polyposis coli mutation – risk factor. Gastric polyps and Duodenal polyps – warrant surveillance. 14

15. Li- Fraumeni syndrome Autosomal dominant. M utation in the tumor suppressor gene p53. Patients at risk for gastric cancer as well as sarcoma, breast cancer, brain tumors, and adrenocortical carcinomas . Lynch syndrome Microsatellite instability. I ncreased risk of gastric and endometrial cancers. 15

16. Cancer genetics Activation of oncogenes. I nactivation of tumor suppressor genes. R eduction of cellular adhesion. R eactivation of telomerase. Presence of microsatellite instability. c-met proto-oncogene -- receptor for the hepatocyte growth factor – frequently overexpressed in gastric cancer. 16

17. Inactivation of the tumor suppressor genes p53 -- in diffuse and intestinal type cancers. Adenomatous polyposis coli gene mutations -- in intestinal type gastric cancers . Reduction or loss in the E-cadherin -- in 50% of diffuse type gastric cancers . Microsatellite instability -- 20% to 30% of intestinal type gastric cancers. 17

18. Molecular subtypes Epstein–Barr virus positive Microsatellite Unstable – best overall prognosis Least recurrence; intestinal type Immunotherapy– most useful Genomically stable Chromosomal instability 18

19. Other risk factors Pernicious anemia Autoimmune – destruction of parietal and chief cells – mucosal atrophy –antral and intestinal metaplasia. ( relative risk of Ca stomach). Polyps Adenomatous polyps– risk. Risk 10 -20% -- increases with size. <2 cm pedunculated , no foci of invasive Ca – endoscopic removal sufficient. >2 cm , sessile, invasive cancer – surgery indicated. Hyperplastic polyps and Peutz-Jeghers syndrome 19

20. Fundic gland polyps Results from glandular hyperplasia and decreased luminal flow Strong association with PPI Dysplasia – rare Excision, cessation of treatment with PPI or regular surveillance – not indicated PPI Block acid – hypergastrinemia – with reserves after stoppage Low acid – more H. pylori – colonise in body – corpus gastritis – astropic gastritis – risk Atropic gastritis reserves on H. pylori eradication. 20

21. PATHOLOGY Dysplasia G astric dysplasia is the universal precursor to gastric adenocarcinoma . S evere dysplasia -- gastric resection if the abnormality is widespread or multifocal, or EMR if the severe dysplasia is localized. M ild dysplasia -- followed with endoscopic biopsy surveillance, and Helicobacter eradication . 21

22. Gross morphology The Borrmann classification system 22 Type I : P olypoid Type II : F ungating T ype III : Ulcerating T ype IV : Diffusely infiltrating growths

23. Lauren classification I ntestinal Environmental Gastric atrophy, intestinal metaplasia Men > women Increasing incidence with age Gland formation Hematogenous spread Microsatellite instability APC gene mutations p53, p16 inactivation D iffuse Familial Blood type A Women > men Younger age group Poorly differentiated, signet ring cells Transmural , lymphatic spread Decreased E-cadherin p53 , p16 inactivation 23

24. World Health Organization histologic typing of gastric cancer Adenocarcinoma Papillary adenocarcinoma Tubular adenocarcinoma Mucinous adenocarcinoma Signet-ring cell carcinoma Adenosquamous carcinoma Squamous cell carcinoma Small cell carcinoma Undifferentiated carcinoma Others 24

25. Early Gastric Cancer Early gastric cancer is defined as adenocarcinoma limited to the mucosa (T1a) and submucosa (T1b) of the stomach . Approximately 70% of early gastric cancers are well differentiated, and 30% are poorly differentiated . The overall cure rate with adequate gastric resection and lymphadenectomy is 95%. 25

26. EARLY GASTRIC CANCER 26

27. SPREAD OF CARCINOMA STOMACH Direct spread The tumour penetrates the muscularis , serosa and ultimately adjacent organs such as the pancreas, colon and liver. Lymphatic spread Both permeation and emboli to the affected tiers of nodes. Unlike malignancies ,nodal involvement does not imply systemic dissemination. Blood-borne metastases This occurs first to the liver and subsequently to other organs, including lung and bone. This is uncommon in the absence of nodal disease. 27

28. Transperitoneal spread Once the tumour has reached the serosa of the stomach and indicates incurability G ive rise to ascites. Palpated either abdominally or rectally as a tumour ‘shelf’. The ovaries may sometimes be the sole site of transcoelomic spread ( Krukenberg’s tumours ). 28

29. DIAGNOSIS AND WORKUP Signs and Symptoms Symptoms – G enerally vague and nonspecific, contributing to its frequently advanced stage at the time of diagnosis. Epigastric pain -- constant and nonradiating and is generally not relieved by eating. early satiety. weight loss. 29

30. Dysphagia and Features of Gastric Outlet Obstruction. Some degree of GI bleeding with Anemia. Paraneoplastic syndromes such as Trousseau’s syndrome (thrombophlebitis ), acanthosis nigricans (hyperpigmentation of the axilla and groin ). A complete history and physical examination should be performed, with special attention to any evidence of advanced disease, including metastatic nodal disease. 30

31. Examination Supraclavicular ( Virchow node ), A xillary ( Irish node ), P eriumbilical ( Sister Mary Joseph node ) Intra abdominal metastases such as hepatomegaly, jaundice , or ascites . Drop metastases to the ovaries ( Krukenberg tumor ) Heme -positive stool and hard nodularity extraluminally and anterior on rectal examination ( Blumer shelf ). 31

32. Screening R egions with high incidence, such as Japan, Korea, and Chile . Modalities for screening are upper endoscopy and barium radiography . Selective screening of patients with specific risk factors -- including gastric polyps/adenomas, pernicious anemia , and certain genetic disorders. 32

33. DIAGNOSTIC EVALUATION AND PREOPERATIVE STAGING The goals of preoperative staging are to Gain information on prognosis, C ounsel the patient effectively, Determine the extent of disease to decide the most appropriate course of therapy . The three main treatment pathways U pfront resection ( with or without subsequent adjuvant therapy) N eoadjuvant therapy followed by resection T reatment of systemic disease without resection 33

34. The main modalities for staging gastric adenocarcinoma Upper endoscopy; EUS ; C ross-sectional imaging such as CT, MRI , and/or positron emission tomography (PET ); D iagnostic laparoscopy. 34

35. Endoscopy and endoscopic ultrasound . It allows visualization of the tumor, provides tissue for pathologic diagnosis, and can help treat patients with obstruction or bleeding. On initial diagnostic endoscopy, if a suspicious mass or ulcer -- adequate tissue to confirm the correct diagnosis histologically . S ix to Eight biopsy specimens from different areas of the lesion. Small lesions (≤2 cm in diameter) -- resected using endoscopic mucosal resection (EMR) or endoscopic submucosal dissection ( ESD) 35

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37. EUS Accurate evaluation of the Depth of tumor invasion, Assessment of perigastric lymph node involvement. Identify involvement of surrounding organs or the presence of ascites. The stomach is filled with water to provide an acoustic window. The stomach wall is visualized as five alternating hypoechoic and hyperechoic layers . 37

38. The mucosa and submucosa represent the first three layers (T1 ). The fourth layer -- muscularis propria , invasion of which signifies a T2 tumor. Expansion of the tumor beyond the muscularis propria causing an irregular border correlates with expansion into the subserosa , or a T3 tumor. The serosa --fifth layer, and loss of this bright line correlates with penetration through it, indicating a T4a tumor . Accuracy: T stage :55 to 88 % ; N stage : 30 to 90% 38

39. Computed tomography . CT of the chest, abdomen, and pelvis with oral and IV contrast agents is a mandatory -- to evaluate for metastatic disease . Accuracy for T staging in 43% to 82 %. Less accurate than EUS for T and N staging. 39

40. Positron emission tomography . Combined PET/CT is more accurate in preoperative staging (68%) than either PET (47 %) or CT (53%) alone . Diffuse and mucinous cancers is limited due to low tracer accumulation . PET-avid tumors can be monitored for a response to neoadjuvant therapy. NCCN guidelines recommend considering PET/CT as part of staging for patients with greater than T1 disease without evidence of metastatic disease on initial CT. 40

41. Staging Laparoscopy and Peritoneal Cytology I ntegral part of the standard workup for gastric cancer . Staging accuracy -- > 95 %. Can avoid unnecessary laparotomy – 9-60 %. CT nondetectable metastasis -- < 5 mm. Approximately 20% to 30% -- T2 or greater gastric cancer and no prior evidence of metastases will be found to have peritoneal disease. 200ml saline instilled all quadrants – shake patient , aspirate at least 50 ml and do cytology – malignant cells seen – M1. 41

42. American Joint Committee on Cancer (AJCC) 42

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46. REFERENCES Bailey and love’s short practice of surgery 28 th edition . Sabistion textbook of surgery 21 st edition . Schwartz Principles of Surgery, 11th edition. 46

47. 47 THANK YOU..