Gastric Malignancy PDF

Gastric Malignancy Stomach (gastric) cancer starts in the antrum cell lining of stomach o Common Benign: Adenoma (Slow growing, starts in epithelial tissue, can become malignant) o Common Malignant: Adenocarcinoma (antrum, most common overall*) Early stage asymptomatic Symptoms in later stages: Men...

Gastric Malignancy Stomach (gastric) cancer starts in the antrum cell lining of stomach o Common Benign: Adenoma (Slow growing, starts in epithelial tissue, can become malignant) o Common Malignant: Adenocarcinoma (antrum, most common overall*) Early stage asymptomatic Symptoms in later stages: Men more likely to get gastric cancer o Indigestion - Diet o Nausea - Lifestyle Habits o Vomiting o Dysphagia - Hormones o GI bleed o Unintentional weight loss Risk factors: o H. pylori o Smoking o Nitrites o Smoked food o Menetrier’s disease o CDH1 (E-cadherin) Treatments: o Surgery (resection) o Chemotherapy o Radiation H Pylori and Gastric Cancer H pylori sticks to surface of epithelial cells via adhesins Urease released to raise pH CagA cytotoxin released o CagA causes chronic inflammation and impairs DNA o H pylori causes gastric cancer in 2 ways 1. Genetic instability increases causing mutations, leading to oncogenesis 2. Deactivation of tumor suppressor genes Smoking and Gastric Cancer Can lead to imbalance btwn damaging factors and defense mechanisms H pylori infection risk increases (w or w/o peptic ulceration), ulceration Carcinogenic compounds induce oncogenesis o Initiates activation of Nicotinic Acetylcholine Receptor (nAChR) § Leads to DNA adduct (dmg): genetic instability leads to oncogenesis and deactivation of tumor suppressor genes § Promotes tumor growth via release of growth factor VEGF § Infection risk increases (H.pylori) increasing pro-inflammatory response/cytokines, induces oncogenesis § Chronic inflammation Nitrites and Gastric Cancer Nitrites = food preservatives for processed meats Nitrites by itself, do NOT cause cancer. Only when reacted with amines Reacts w amines in the stomach o Forms nitrosamines (carcinogen) that increases pro-inflammatory and cancer response § Causes DNA dmg in stomach § Causes dysbiosis of microbiota Nitrites also cause an increase risk of H pylori Management: o Consume less processed foods o High fiber foods Smoked foods and Gastric Cancer Carcinogenic compounds introduced to food: PAH and HCA (Polycyclic aromatic hydrocarbon and heterocyclic amine) that are produced due to high heat o DNA damage o Increase immune response o Initiate cancer response Management: Consume foods prepared w natural smoking, w/o added chemicals or preservatives o Eat more complex carbs, fruits and vegetables Menetrier Dz and Gastric Cancer Characterized by giant mucosal folds in PROXIMAL stomach (cardia/fundus) Hypertrophic gastropathy from overexpression of TGF-a (TGF-a assc with tumor initiation and growth) Complications: o â Acid (leading to indigestion) o â Albumin (leading to hypo-albuminemia) Risk of GC increases if following additional factors present: o Chronic inflammation o Change in gastric mucosa o Family hx o H pylori E-Cadherin gene (CDH1) and Gastric Cancer Normally allows for proper cell to cell adhesion Mutation will NOT allow adhesion à DYSPLASIA occurs that leads to gastric cancer Adenocarcinoma Most common malignant cancer that is defined by: Depth of invasion, Histology, Growth pattern Depth of invasion Histology Early Intestinal (type) Mucosa Submucosa Gland shape Late Diffuse (type) Beyond submucosa Depth of invasion Early Mucosa Submucosa Late Beyond submucosa Signet ring Growth Pattern Borrmann classfication Bulky tumors with glandular structures Well-differentiated cells (2 types) o Tubular adenocarcinoma o Papillary adenocarcinoma More common in middle aged men Risk factors: o Diet high in smoked and salted foods o Pickled vegetables o Lack of citrus fruit or green leafy vegetables o Low socioeconomic status o Cigarette smoking Assc with: o Chronic gastritis (intestinal metaplasia is a precursor lesion) o H pylori infection o Autoimmune gastritis o Partial gastrectomy (side effect: reflux) o Gastric adenomas Histology Intestinal type Gland shape Diffuse type Signet ring Also known as “Linitis Plastica”/”Signet Ring Adenocarcinoma” Starts in stomach then reaches other parts of the body (ex. ovaries) Poorly differentiated cells (signet ring appearance) Seen in 48yo men, women, more common in young No known risk factors o Can be related to E-cadherin gene (CDH1) causing dysplasia o Hereditary diffuse gastric cancer (rare autosomal dominant) Will have thickened, rubbery, hard gastric walls w signet ring cells Krukenburg (Ovarian) tumor: o Mucin-filled signet ring cells o Cellular stroma background (fibroblast) Remember diffuse adenocarcinoma starts in stomach then reaches other parts of the body (ex. ovaries) Growth Pattern Borrmann classfication For classifying macroscopic appearance of gastric cancer Tumor Type & Kind Borrmann Classification Appearance Polyploid tumors Type I Fungated carcinoma Type II Ulcerated carcinoma Type III Infiltrating carcinoma Type IV - Early cancer stage - Minimal invasion into mucosa/submucosa - Well defined borders - Lobulated surface - Stomach is protruded - Raised margins - shallow ulceration - elevated edges - Invasion deep into submucosa - Infiltration of tumor cells - Irregular borders - no raised margin - Most progressive - High infiltrating malignant cells - Leathery Bottle-like/Linitis plastica appearance Other Gastric malignancies: GIST, NET, Lymphoma (MALT, Diffuse Large B-cell) GastroIntestinal Stromal Tumors (GIST) Soft tissue sarcoma (in tissue and bones, nerves are soft tissue, this is a nerve cell tumor) Nerve cells are found in the walls of the stomach and other digestive organs Cell of origin: interstitial cell of Cajal o Located in the muscularis propria wall of the GI tract o ICCs called the “pacemakers” of GI tract b/c they signal muscles in GI to contract and move food and liquid along GIST risk is increased when assc with: o Neurofibromatosis type 1: café au lait spots and neurofibromas (soft bumps) o Carney’s triad § Gastric GIST § Paraganglioma § Pulmonary chondroma Pathogenesis via ‘gain of function’ mutations: o ~70-80%: in the receptor tyrosine kinase gene c-KIT (CD117) o ~10%: in platelet-derived growth factor receptor-alpha (PDGFR-alpha) Normally, PDGFR is a Tyrosine kinase Morphology: o Gross submucous mass w giant ulceration w blood allows for cell-cell signaling o Solitary, well-circumscribed, fleshy mass Mutation of c-KIT and PDGFR-a produces o Covered by ulcerated or intact mucosa intracellular signaling to: GIST Histology (3 forms) - Promote tumor cell proliferation Cell Type % in matrix Appearance - Inhibit tumor suppressor genes (CDKN2A) Spindle Cell 70% Elongated Nuclei Epithelioid Cell 20% Round Nuclei Mixed 10% Treatment for GIST: Total resection, targeted therapy (Imatinib: specific for tumors) NETs or Carcinoid: Well-Differentiated Neuroendocrine Tumor Cancer of neuroendocrine cells Neuroendocrine cells found in: Mnemonic: toothless Lancelot said PAS o Thyroid o Lungs o Stomach o Pancreas o Adrenal Gland o Small bowel Rare, complex Overexpression/high levels of bio-markers Chromogranin A (B-cells of pancreas) and Synaptophysin Assc with: o Hyperplasia autoimmune chronic atrophic gastritis o MEN1- Multiple Endocrine Neoplasia type 1: two or more endocrine glands have tumor o Zollinger-Ellison (pancreatic tumor: high acidity, lower bicarb secretion) Important prognosis factor: Location o Foregut Carcinoid § In stomach, duodenum proximal to ligament of Treitz, esophagus § Rarely metastasize, generally cured by resection § Least progressive o Midgut Carcinoid § In jejunum and ileum § Often multiple § Most aggressive o Hindgut Carcinoid § In appendix and colorectum § Discovered incidentally Endoscopic features: o Small, sharply outlined, covered by flattened mucosa Histology: o Bland nuclei with salt and pepper chromatin o Rare mitosis o Prominent vessels o No necrosis Treatment: o Surgical resection o Peptide receptor radionucleotide therapy (PRRT) given through IV that targets the somatostatin receptor Lymphoma (Tumor derived from lymphocytes) Cancer of immune cells o 55-75% of primary gastrointestinal lymphomas are gastric o 1-7% of gastric malignancies o Most patients are men > 60 years old Most common lymphoma: o Mucosa-associated lymphoid tissue (MALT) gastric lymphoma from H. pylori o Diffuse large B-cell gastric lymphoma Assc w: o Erosion o Intestinal metaplasia o H. pylori o Atrophy and dysplasia MALT Lymphoma o Extranodal lymphoma found outside of lymph nodes o Associated with chronic gastritis and H. Pylori infection affecting the antrum o Clinically indolent (slow progression, painless) o Pathogenesis: § When left untreated: — Persistent presence of the infection leads to prolonged activation of B cells — Leads to uncontrolled proliferation § Diffuse infiltrate of small B-cells and small lymphocytes and small plasma cells § Over time, B cells in MALT acquire genetic mutations promoting growth and survival leading to malignancy § Diffuse lymphoplasmacytic infiltrate § Composed of small, mature B lymphocytes with small plasma cells o Treatment (same as DLBCL): § Depends on stage, location, pt’s health § Antibiotics, surgery, radiation, chemotherapy, targeted therapy Diffuse Large B Cell Lymphoma (DLBCL) o Nodal and Extranodal lymphoma (in lymph and outside of lymph) o May arise from MALT lymphoma or de novo o May co-exist with MALT lymphoma o AGGRESSIVE (rapid progression) o Assc with: § Epstein-Barr Virus (EBV) § H. pylori § Autoimmune disorders o Diffuse infiltrate of high-grade, centroblast-like cells o Pathogenesis: § Genetic mutations disrupt normal B-cell function, contribute to uncontrolled growth § Abnormalities in B cell receptor (BCR) signaling pathways leads to uncontrolled cell proliferation and survival § Certain viruses, such as EBV, can alter B-cell signaling and promote cell survival Histology: o The lymphoma cells are large with vesicular nuclei entrapping a gastric gland o Centroblast-like cells Endoscopy: o Gastroscopy show multiple gastric folds, different size, and many ulcerative lesions in the gastric mucosa Treatment (same as MALT): o Depends on stage, location, pt’s health o Antibiotics, surgery, radiation, chemotherapy, targeted therapy Surgical Procedures: Gastrectomy 2 types: o Total: surgical removal of all the stomach o Partial: surgical removal of part of the stomach § Pylorus preservation depends on the part of the stomach removed § If cancer is present, then pylorus is removed Performed as a treatment for stomach cancer, may also be indicated for a bleeding gastric ulcer or a perforation in the stomach wall Roux-En-Y Gastric Bypass Only decreases load on stomach It is NOT a solution for cancer Staples placed in the stomach, creating a small pouch in the upper section, and part of the small intestine is divided and attached directly to the stomach pouch After gastric bypass: o Swallowed food goes into small pouch of stomach then directly into small intestine o Bypasses most of your stomach and the first section of your small intestine. Billroth I, II and Gastrectomy Billroth overview: o Partial resection of the stomach with anastomosis to duodenum (type I) or to jejunum (type II) o Standard treatment for ulcer disease, stomach cancer, injury and other diseases of the stomach Billroth I o Gastroduodenostomy o Involves partial gastrectomy (removal of antrum and pylorus with anastomosis of gastric stump to duodenum Billroth II o Gastrojejunostomy o Involves partial gastrectomy (removal of antrum and pylorus with anastomosis of gastric stump to jejunum Gastrectomy Complications *Know definitions Anastomotic Leak: Leak at the attachment site Bile reflux: Bile flows backward into your stomach or esophagus Dumping syndrome: Food travels to your small intestine before its broken down Malnutrition: not getting enough of the right nutrients Internal hernia: parts of small intestine bulges through membrane that attaches intestine to abdominal wall Narrowing at the attachment site: the site that connects partial stomach or esophagus and small intestine narrows Post-surgery gastroparesis: The stomach doesn’t process food as quickly as it should (Gastroparesis = stomach paralysis) Recovery time for Gastrectomy (major surgery): - Requires 2 mo to heal - Regaining energy levels and getting used to the new eating habits takes ~ 3 to 6 months or even longer