4. Gastric Cancer.pptx666666666666666666666666666

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1. GASTRIC CANCER By: Dr. J. K. Sesay Senior Registrar, MOHS Specialist: General Surgeon Dip. Int. Health, M.D., M.Med . Surgery USLTHC, Connaught

2. OUTLINE Summary Classification Epidemiology Etiology Clinical features Subtypes and variants Diagnostics Pathology Differential diagnosis Treatment Complications Prognosis References

3. SUMMARY Gastric cancer refers to  neoplasms  in the  stomach , including cancers of the esophagogastric junction. The  incidence  is declining in the United States and Europe, while it is rising in Japan and South Korea. Gastric cancer is associated with several  risk factors  (e.g., consumption of foods high in  nitrates , increased  nicotine  intake,  Helicobacter pylori  infection). In its early stages, the disease is often asymptomatic or accompanied by nonspecific symptoms (e.g., epigastric discomfort,  postprandial  fullness, or nausea). Late-stage disease may present with  gastric outlet obstruction  (mechanical obstruction of the  pyloric canal ), leading to weight loss and vomiting.  Biopsy  during endoscopy confirms the diagnosis.  Adenocarcinomas  are the most common form of gastric cancer. Treatment includes endoscopic or surgical resection. Depending on staging,  chemotherapy  may be indicated before or after surgery ( neoadjuvant  or adjuvant  chemotherapy ), or as a  palliative therapy .

4. PATHOLOGY OF GASTRIC CARCINOMA TYPES Borrmann’s Classification Type I: for the well-circumscribed polypoid lesions Type II: for polypoid tumors with marked central ulcerations Type III: for the ulceration tumors with infiltrative margins Type IV: for the LINITIS PLASTICA ( stomach wall becomes thicker and more rigid )

5. EPIDEMIOLOGY Sex:  ♂  >  ♀ Peak  incidence : 70 years Geographical distribution: strong regional differences High  incidence  in South Korea and Japan Declining  incidence  in the United States and Europe

6. ETIOLOGY Exogenous   risk factors Diet rich in  nitrates  and/or salts (e.g., dried, preserved food)  Nicotine  use Low socioeconomic status Endogenous   risk factors Diseases associated with a higher risk of gastric cancer Atrophic gastritis H. pylori  infection: associated with a higher risk of  intestinal gastric cancer  but not with  diffuse gastric cancer Gastric ulcers Partial gastrectomy Gastroesophageal reflux disease  ( GERD ; for cancers of the  gastroesophageal junction ) Adenomatous gastric polyps Hereditary factors (positive  family history , hereditary non‑polyposis  colorectal cancer ) Higher  incidence  in individuals with  blood type A .

7. CLINICAL FEATURES Gastric cancer is often asymptomatic. Early signs are nonspecific and often go unnoticed. At later stages the following symptoms may occur: General signs Weight loss Chronic  iron deficiency   anemia  (paleness, fatigue,  headaches ) Gastrointestinal signs Abdominal  pain Early satiety Nausea or vomiting Dysphagia Acute gastric bleeding ( hematemesis or  melena )

8. Clinical features contd. Late-stage gastric cancer: Palpable  tumor  in epigastric region Gastric outlet obstruction Hepatomegaly ,  ascites Troisier’s sign -: Virchow's node: left supraclavicular adenopathy , located where the  thoracic duct  joins the  subclavian vein  at the  venous angle . Sister Mary Joseph's node : umbilical node indicating  metastasis  from a gastrointestinal or abdominopelvic  malignancy Malignant acanthosis nigricans  (associated with gastric  adenocarcinoma )

9. Troisier’s sign Troisier's sign is the finding of a palpable left supraclavicular lymph node; this is called Virchow's node. It may indicate gastrointestinal malignancy, commonly of the stomach, or less commonly, lung cancer.

10. Sister Mary Joseph's node Sister Mary Joseph's nodule  refers to a palpable  nodule  bulging into the umbilicus as result of a malignant cancer in the abdomen or pelvis. It is associated with multiple peritoneal metastases and usually indicates an advanced stage of disease with a poor prognosis. It can be painful at times.

11. SUBTYPES AND VARIANTS METASTATIC  DISEASE Lymphangitic  spread All local  lymph nodes  (lesser and  greater curvature ) Celiac, paraaortic, and  mesenteric   lymph nodes Carcinoma  of the  cardia  may spread to  mediastinal lymph nodes . Hematogenous spread to  liver ,  lung , skeleton, brain Local invasion of adjacent structures Peritoneal carcinomatosis Esophagus ,  transverse colon ,  pancreas , etc. Direct seeding To the  ovaries  ( Krukenberg tumor ): an ovarian  malignancy  comprised of  signet ring cells ( is a  cell  with a large vacuole )  that has  metastasized  from a primary site, most commonly the  stomach To the  pouch of Douglas

12. KRUKENBERG TUMOR Krukenberg tumor is a metastatic disease to the ovaries composed of mucin-rich signet-ring cells. The most common primary site for this tumor is the stomach. These tumors spread most likely through the lymphatic channels.

13. DIAGNOSTICS Diagnostic procedures Upper endoscopy  with  biopsy  (best initial test)  :  Biopsy  confirms the diagnosis Barium  upper GI series  may be considered and would show loss of intestinal folds and stenosis  Laboratory test Iron deficiency   anemia   Serologic markers  Tumor necrosis factor – alpha (TNF- α )   as possible future  tumor marker  

14. Diagnostics contd. Staging Abdominal  ultrasound   Endosonography Assessment of  tumor  depth and local  lymph nodes Abdominal and pelvic  CT-scan  using intravenous and oral contrast; Thoracic  CT-scan   Diagnostic laparoscopy  

15. Gastric cancer Endoscopy view of the gastric antrum There is a gastric mass at the level of the lesser curvature with an irregular margin (perimeter marked by green outline) and central ulceration (green overlay). These findings are consistent with gastric cancer.

16. MANAGEMENT OF GASTRIC ADENOCARCINOM Management of gastric adenocarcinom

17. Gastric cancer Fluoroscopy of the stomach (with oral contrast) and CT abdomen (axial; with IV contrast) The gastric wall is thickened and irregular (green overlay) with an abnormal narrowing. These findings are consistent with gastric cancer with stenosis.

18. PATHOLOGY Adenocarcinoma  (90% of cases) Typically localized,  exophytic  lesion +/- ulceration Arise from glandular cells in the  stomach ; usually located on the  lesser curvature of the stomach Signet ring cell carcinoma Diffuse growth Multiple  signet ring cells  = round cells filled with  mucin , with a flat  nucleus  in the cell periphery Less common Adenosquamous  carcinoma Squamous cell carcinoma

19. DIFFERENTIAL DIAGNOSIS Gastric ulcer Gastroesophageal reflux disease  ( GERD ) MÉNÉTRIER'S DISEASE (Giant hypertrophic gastritis): gastritis  featuring massive enlargement of the  mucosal  folds Non-ulcer   dyspepsia Other types of cancer mucosa-associated lymphoid tissue ( MALT) lymphoma Sarcoma: a malignant cancer of cells of mesenchymal origin (e.g., cartilage, fat, muscle) Gastrointestinal stromal tumor ( GIST )

20. Gastrointestinal stromal tumor Endoscopy of the stomach (pyloric window) A submucosal mass (green overlay) with an intact gastric mucosa can be seen within the gastric body. This finding is consistent with gastric lipoma, gastrointestinal stromal tumor (GIST), or fibroma of the stomach. Further diagnostics confirmed a GIST. P: pylorus; C: gastric body

21. Liver metastasis of a gastrointestinal stromal tumor (GIST) Ultrasound of the liver A round, hyperechoic lesion (circled in green) with a hypoechoic margin (green overlay) can be seen within the liver parenchyma. There are two hypoechoic areas in the center of the lesion (red overlay), which likely indicate central necrosis. The hypoechoic margin is also referred to as the halo sign and is a typical feature of a malignant lesion on liver ultrasound. These findings are consistent with liver metastasis of a gastrointestinal stromal tumor

22. TREATMENT Exact therapy, which may be either curative or palliative, depends on staging and the type of  tumor . Endoscopic resection  Surgery Perioperative  chemotherapy , sometimes  radiotherapy Trastuzumab ( a monoclonal antibody against the HER2 tyrosine kinase receptor that inhibits cellular signaling and causes cytotoxicity )  is indicated for  HER2+( human epidermal growth factor receptor 2, a growth-promoting protein on the outside of all breast cells )  gastric  adenocarcinomas  

23. Treatment contd. Surgery Radical gastrectomy and lymphadenectomy (operative standard)  Resection of the lesser and  greater omentum  and radical lymphadenectomy Roux-en-Y gastric bypass The  surgeon  separates the  proximal   jejunum  from the  duodenum  and creates an end-to-end  anastomosis  of the  jejunum  with the remaining part of the  stomach  (gastrojejunostomy), or in the case of a total gastrectomy, with the  esophagus  (esophagojejunostomy). Duodenal  stump is connected distally with the  jejunum  using an end-to-side  anastomosis .  Alternative: subtotal gastrectomy 

24. Total gastrectomy (with Roux-en-Y anastomosis) Total gastrectomy w/ blind closure of duodenal stump (left): - Removal of the stomach leaving the distal esophagus and proximal duodenum open - The duodenal stump (purple line) is closed Roux-en-Y anastomosis (right): - A segment of the proximal jejunum is divided (blue and green dashed lines) - Creation of esophagojejunostomy: The distal cut end of the jejunal loop is anastomosed via an end-end with the distal esophagus (green dashed line) - Creation of jejunojejunostomy: The proximal jejunal stump is anastomosed end-to-side to a distal jejunal loop (blue dashed line), this anastomosis is made distal to the esophagojejunostomy site to prevent bile reflux

25. Subtotal gastrectomy (with Roux-en-Y anastomosis) Subtotal gastrectomy: - Subtotal gastrectomy involves the resection of the body and pyloric channel of the stomach (transparent portion of the stomach in this image). - The cardia and fundus of the stomach and their blood supply is preserved (opaque portion of the stomach here). - The duodenal stump (dashed red line) is closed. Roux-en-Y anastomosis: - A segment of the proximal jejunum is divided. - Gastrojejunostomy creation: The distal cut end of the jejunal loop (black I) is anastomosed side-to-side to the gastric stump (purple dashed line; I–I). - Jejunojejunostomy creation: The proximal jejunal stump (green II) is anastomosed end-to-side to a distal jejunal loop (green dashed line, II–II).

26. COMPLICATIONS Malignant acanthosis nigricans A  paraneoplastic syndrome: a group of rare disorders that are triggered by an abnormal immune system response to a cancerous tumor known as a "neoplasm."   seen in  adenocarcinomas  of GI origin, especially in gastric  adenocarcinoma Pathophysiology: caused by  exogenous  transforming growth factor  TGF- α   and  epidermal growth factor  (GF) Clinical findings Brown to black,  intertriginous  and/or nuchal  hyperpigmentation  that can turn into itching, papillomatous, poorly-defined efflorescence Rapid growth and  verrucous  or papulous surface helps to differentiate it from  benign acanthosis nigricans Localization:  axilla , groin, neck

27. Acanthosis nigricans Hyperpigmentation, hyperkeratosis, and numerous skin tags (papillomatosis) are visible on the right axilla. These findings are consistent with acanthosis nigricans

28. Complications contd.: Postgastrectomy syndromes Related to resorption Maldigestion Consequences and management Iron deficiency  → supplement  iron Pernicious anemia  due to lack of  intrinsic factor , usually produced by  gastric parietal cells  → supplement  vitamin B 12

29. Related to  anastomosis Small intestinal bacterial overgrowth ( SIBO )Definition: bacterial overgrowth within the  small intestine Causes Anatomic abnormalities: (e.g., surgery causing blind intestinal loops – blind loop syndrome ), strictures Motility disorders  Pathophysiology: bacterial overgrowth → bacteria deconjugate  bile acids , increase  vitamin B 12  turnover, and produce increased amounts of  vitamin K  and  folic acid Clinical features:  diarrhea ,  steatorrhea , weight loss,  malabsorption  (e.g.,  deficiency of vitamin B 12 , A, E, D,  zinc , and  iron ) Diagnostics Jejunal  aspirate cultures collected during endoscopy  Positive  lactulose breath test   Treatment:  antibiotics  and parenteral supplementation of  vitamins  and  proteins , possibly surgical treatment

30. Related to motility Dumping syndrome:  rapid gastric emptying due to either defective gastric reservoir function or  pyloric  emptying mechanism, or anomalous post-surgery gastric motor functions. Early dumping Cause: rapid emptying of undiluted  chyme  into the  small intestine  caused by a dysfunctional or bypassed  pyloric sphincter   Clinical features Appears within 15–30 minutes after ingestion of a meal Symptoms may include nausea, vomiting,  diarrhea , and cramps, as well as vasomotor symptoms such as sweating,  flushing , and  palpitations . Management Dietary modifications: Small meals that include a combination of complex  carbohydrates  and foods rich in protein and fat to cover protein and energy requirements are preferable. 30–60 min of rest in the  supine position  after meals  Often spontaneous improvement after a couple of months

31. Related to motility contd . Late dumping   Cause :  postprandial hypoglycemia ; dysfunctional  pyloric sphincter  →  chyme  containing glucose immediately reaches the  small intestine  → glucose is quickly resorbed →  hyperglycemia  → excessive release of  insulin  →  hypoglycemia  and release of  catecholamines Treatment Dietary modifications OCTREOTIDE ( a somatostatin analog that inhibits growth hormone secretion and causes splanchnic vasoconstriction via decreased secretion of vasodilatory peptides such as glucagon )  and surgery are second and third-line therapies

32. PROGNOSIS Since there are no early signs, gastric cancer is often diagnosed very late. At diagnosis, 60% of cancers have already reached an advanced stage that does not allow for curative treatment. Early gastric cancer has the best prognosis . Distant  metastases  or  peritoneal carcinomatosis  dramatically worsen the prognosis and are lethal most of the time.

33. REFERENCES 1. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention. Cancer Epidemiol Biomarkers Prev .2014; 23(5): p.700-713. doi:  10.1158/1055-9965.EPI-13-1057 . | Open in Read by QxMD 2. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education; 2015 3. Chan AOO, Wong B. Risk factors for gastric cancer. In: Post TW, ed. UpToDate .Waltham, MA: UpToDate. https://www.uptodate.com/contents/risk-factors-for-gastric-cancer?source=search_result&search=gastric%20cancer&selectedTitle=2~150 . Last updated September 26, 2016. Accessed January 31, 2017. 4. Tsugane S. Salt, salted food intake, and risk of gastric cancer: Epidemiologic evidence. Cancer Sci .2005; 96(1): p.1-6. doi:  10.1111/j.1349-7006.2005.00006.x . | Open in Read by QxMD 5. Ladeiras-Lopes R, Pereira AK, Nogueira A, Pinheiro-Torres T, Pinto I, Santos-Pereira R, Lunet N. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control .2008; 19(7): p.689-701. doi:  10.1007/s10552-008-9132-y . | Open in Read by QxMD 6. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017