Gastrointestinal cancers Notes

NOTES NOTES GASTROINTESTINAL CANCERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Tumors arising from cells in gastrointestinal (GI) tract ▪ Multifactorial etiology; generally result from aberrant cellular signaling, unregulated cellular growth ▫ Genetic alterations (e.g. point mutations, amplifications, rearrangements, deletions) ▫ Epigenetic influence (e.g. DNA methylation, chromatin remodeling) ▫ Environmental factors (e.g. exposure to carcinogens, chronic inflammation) ▪ Risk increases with age SIGNS & SYMPTOMS ▪ Highly variable clinical presentation; see individual disorders ▪ Fatigue, anorexia, weight loss DIAGNOSIS ▪ Grading, TNM staging for treatment ▫ T: characteristic of primary Tumor (e.g. invasion of nearby tissue) ▫ N: involvement of regional lymph Nodes ▫ M: Metastasis; spread from primary tumor to other body parts LAB RESULTS Biopsy ▪ Histopathological diagnosis TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ See individual disorders OTHER INTERVENTIONS ▪ Radiation therapy DIAGNOSTIC IMAGING Imaging studies ▪ Localization, staging OSMOSIS.ORG 237

CARCINOID TUMOR osms.it/carcinoid-tumor PATHOLOGY & CAUSES ▪ Uncommon, well-differentiated, slowgrowing neuroendocrine tumor; originates in tubular digestive tract; also found in bronchopulmonary system, genitourinary tract ▪ Benign/malignant; tendency for liver metastasis ▪ Carcinoid: tumors of different morphology, less aggressive than GI tract adenocarcinomas; low grade (proliferative activity); low mitotic rate TYPES ▪ Embryonic origin of GI tract (e.g. foregut, midgut, hindgut) Foregut tumors (e.g. stomach) ▪ Type I ▫ Most common ▫ Originates from enterochromaffin-like (ECL) cells ▫ In association with high gastrin levels secondary to chronic atrophic gastritis ▫ Small, usually benign ▪ Type II ▫ Originates from ECL cells ▫ In association with high gastrin levels induced by gastrinomas (e.g. Zollinger– Ellison syndrome) in conjunction with multiple endocrine neoplasia type 1 (MEN1) ▫ Often large, indolent; low-grade malignancy ▪ Type III ▫ Not associated with high gastrin levels ▫ Large, aggressive; local lymphatic/ hepatic metastases; produce serotonin (5-HT) Midgut tumors ▪ Small bowel (most common) ▫ Originates from intraepithelial endocrine 238 OSMOSIS.ORG cells ▫ Commonly located in ileum; may arise from Meckel’s diverticulum ▫ Potential for lymph node/hepatic metastasis ▪ Appendix ▫ Originates from subepithelial endocrine cells ▫ Relatively low potential for metastasis Hindgut tumors ▪ Rectum, colon, cecum (most common) COMPLICATIONS ▪ Depend on tumor’s location, size, local biochemical attributes ▫ Local/distant metastasis ▫ Pain: obstruction, intussusception, bowel ischemia, mechanical pressure from tumor ▫ Desmoplasia: intense, local reaction characterized by overproduction of extracellular matrix proteins + myofibroblast cell proliferation → fibrosis, obstruction ▫ Carcinoid syndrome: tumor-related humoral factors (e.g. serotonin, histamine, etc.) → cutaneous flushing, pruritic rash; excessive lacrimation; wheezing; diaphoresis SIGNS & SYMPTOMS ▪ Often asymptomatic, discovered incidentally (e.g. imaging, surgery, endoscopy) ▪ Vary according origin site ▫ Nonspecific, vague abdominal pain ▫ Loss of appetite, vomiting, diarrhea, constipation ▪ Desmoplasia (with CT scan)

Chapter 32 Gastrointestinal Cancers DIAGNOSIS TREATMENT DIAGNOSITC IMAGING MEDICATIONS CT scan, MRI, labeled somatostatin receptor-based diagnostic imaging ▪ Localization, TNM staging ▪ Presence of hepatic lesions SURGERY Endoscopy with biopsy ▪ Tumor visualization ▪ Histopathological analysis, grading ▪ Somatostatin analogues suppress tumor proliferation, decrease symptoms ▪ Surgical removal of tumor LAB RESULTS ▪ 5-hydroxyindoleacetic acid, chromogranin Figure 32.2 Gross pathology of carcinoid tumor of the terminal ileum. Figure 32.1 Histological appearance of a carcinoid tumor of the lung. MNEMONIC: CARCinoid Carcinoid syndrome components Cutaneous flushing Asthmatic wheezing Right-sided valvular heart lesions Cramping and diarrhea OSMOSIS.ORG 239

CHOLANGIOCARCINOMA osms.it/cholangiocarcinoma PATHOLOGY & CAUSES ▪ Rare bile duct cancers; arise from epithelial cells of intrahepatic, extrahepatic bile ducts (not including gallbladder, ampulla of Vater) ▪ High fatality due to late diagnosis; highly proliferative ▪ Mostly adenocarcinomas; minority squamous cell carcinomas TYPES ▪ Determined by location (Bismuth–Corlette) Type I ▪ Located below confluence of left, right hepatic ducts Type II ▪ Located at confluence Type IIIa ▪ Occludes common hepatic duct Type IIIb ▪ Occludes right/left hepatic duct Type IV ▪ Multicentric (IDH1) ▪ Risk increases with age ▪ Slightly more common in individuals who are biologically male COMPLICATIONS ▪ Metastasis ▫ Liver, lymph nodes, peritoneum, bone, etc. ▪ Bowel perforation, bleeding SIGNS & SYMPTOMS ▪ Often asymptomatic initially; malaise, weight loss, abdominal pain ▪ Extrahepatic disease (when bile drainage obstructed) ▫ Right upper quadrant pain, jaundice, pruritus, dark urine, clay-colored stools, weight loss ▪ Intrahepatic disease ▫ Dull right upper quadrant pain, malaise, weight loss ▪ Other findings ▫ Hepatomegaly, palpated mass RISK FACTORS ▪ Primary ▫ Existing liver, gallbladder disease: primary sclerosing cholangitis (PSC); chronic liver disease (e.g. viral hepatitis, cirrhosis) ▪ Congenital abnormalities of biliary tree ▪ Genetic disorders ▫ Lynch syndrome; multiple biliary papillomatosis ▪ Obesity ▪ Liver fluke infection (undercooked fish) ▪ Intrahepatic cholangiocarcinomas ▫ Associated with mutations in gene encoding isocitrate dehydrogenase 1 240 OSMOSIS.ORG Figure 32.3 Histological appearance of a cholangiocarcinoma. There are normal hepatocytes in the top left of the image, with the tumour occupying the bottom right of the image.

Chapter 32 Gastrointestinal Cancers DIAGNOSIS ▪ History, physical examination ▫ Consistent with hepatobiliary disease DIAGNOSTIC IMAGING MRI, CT scan, PET, etc. ▪ Detailed evaluation of lesion TNM staging Transabdominal/endoscopic ultrasound (EUS) with biopsy ▪ Biliary obstruction, dilation of intrahepatic ducts ▪ Histolopathological analysis, grading LAB RESULTS ▪ Tumor markers ▫ Carbohydrate antigen (CA) 19-9; carcinoembryonic antigen (CEA) ▪ Liver function tests ▫ Consistent with biliary obstruction, cholestasis ▫ Elevated transaminases, gammaglutamyl transpeptidase, alkaline phosphatase ▫ Prolonged prothrombin time/elevated INR ▫ Elevated bilirubin Figure 32.4 Histological appearance of a cholangiocarcinoma. This image shows the tumor edge, with normal hepatocytes on the right and tumor on the left. The tumor cells form tubular structures and are surrounded by fibrosis. TREATMENT MEDICATIONS ▪ Fluoropyrimidine-based chemoradiotherapy ▪ Chemotherapy SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Radiation OSMOSIS.ORG 241

COLORECTAL CANCER osms.it/colorectal-cancer ▪ Common malignancy of large bowel/rectum ▪ Third most common cancer worldwide ▪ Often arises from colonic epithelial tissue → adenomatous polyp formation → adenocarcinoma ▪ High metastatic potential after penetrating muscularis mucosa ▪ Black people of African descent ▫ Highest rates in United States ▪ More common in individuals who are biologically male ▪ Risk increases with age ▪ Protective factors ▫ Physical activity; regular use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) RISK FACTORS COMPLICATIONS PATHOLOGY & CAUSES ▪ Hereditary ▫ Familial adenomatous polyposis; Lynch syndrome, MUTYH-associated polyposis ▪ Inflammatory bowel disease ▪ Lifestyle ▫ Smoking, physical inactivity ▪ Dietary ▫ High alcohol consumption; processed red meat; low consumption of fruits, vegetables ▪ Obesity ▪ Diabetes mellitus, insulin resistance ▪ Low socioeconomic status ▪ History of abdominal radiation ▪ Lack of screening colonoscopy ▪ ▪ ▪ ▪ ▪ Iron-deficiency anemia (due to bleeding) Local, distant metastasis Bowel obstruction Cachexia Bowel perforation → peritonitis SIGNS & SYMPTOMS ▪ May be asymptomatic initially ▪ Vague constitutional symptoms ▫ Fatigue, anorexia, weight loss ▪ Change in bowel habits ▫ Narrowing of stool, constipation, diarrhea ▪ Rectal bleeding ▫ Frank/occult ▪ Rectal pain, tenesmus (feeling of incomplete defecation) ▪ Nausea, vomiting ▫ Bowel obstruction from advanced malignancy DIAGNOSIS DIAGNOSTIC IMAGING Figure 32.5 Gross pathology of an exophytic colorectal carcinoma. 242 OSMOSIS.ORG Colonoscopy/flexible sigmoidoscopy; biopsy, CT colonography ▪ Tumor visualization, histopathological analysis, grading, TNM staging, potential for resection

Chapter 32 Gastrointestinal Cancers TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Polypectomy with clear margins ▪ Surgical resection ▪ Sessile polyps: colectomy Figure 32.6 Histological appearance of adenocarcinoma of the colon. The tumor is composed of malignant cells which continue to form glandular structure. The left side of the image displays normal colonic mucosa. OTHER INTERVENTIONS ▪ Chemoradiation therapy LAB RESULTS ▪ Tumor marker: CEA ▪ Stool guaiac testing ▫ Positive for occult blood OTHER DIAGNOSTICS Digital rectal exam ▪ Palpable mass if distal rectal mass Figure 32.7 A CT scan in the axial plane demonstrating a tumor in the cecum. Figure 32.8 Positron emission tomography with high levels of tracer accumulation in the pelvis (rectal tumor) as well as the liver and kidneys (metastases). OSMOSIS.ORG 243

ESOPHAGEAL CANCER osms.it/esophageal-cancer PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Rare malignancy of esophageal epithelium ▪ Squamous cell carcinoma (most common)/ adenocarcinoma ▪ Commonly diagnosed when disease advanced ▪ Tendency for rapid metastasis ▪ Asymptomatic initially; dysphagia; pyrosis; retrosternal pain; weight loss ▪ Late symptoms ▫ Coughing, chest discomfort when swallowing; hiccups if spread to diaphragm CAUSES ▪ Chronic exposure to irritants → metaplasia → dysplasia → malignant transformation RISK FACTORS ▪ Smoking ▪ Alcohol (esp. combined with smoking) ▪ Gastroesophageal reflux disease (GERD); reflux esophagitis, Barrett esophagus ▪ Hiatal hernia ▪ More common in individuals who are biologically male ▪ Risk increases with age MNEMONIC: ABCDEF DIAGNOSIS DIAGNOSTIC IMAGING EUS guided biopsy, CT scan, PET, integrated fluorodeoxyglucose (FDG) ▪ Tumor visualization, histopathological analysis, grading, TNM staging, potential for resection Bronchoscopy ▪ In carina identifies potential lung involvement OTHER DIAGNOSTICS ▪ Palpable supraclavicular lymphadenopathy Esophageal cancer risk factors Achalasia Barret’s esophagus Corrosive esophagitis Diverticulitis Esophageal web Familial COMPLICATIONS ▪ Esophageal obstruction; regurgitation → aspiration → aspiration pneumonia; metastasis 244 OSMOSIS.ORG Figure 32.9 Endoscopic appearance of an esophageal tumor. The tumor sits at the gastroesophageal junction and is viewed from above.

Chapter 32 Gastrointestinal Cancers TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Resection of primary tumor, associated nodes OTHER INTERVENTIONS ▪ Radiation Esophageal stenting ▪ Therapeutically enlarges esophageal lumen, reduces dysphagia Figure 32.10 A barium swallow demonstrating a tumor distorting the normal outline of the esophagus. GALLBLADDER CANCER osms.it/gallbladder-cancer PATHOLOGY & CAUSES ▪ Uncommon malignancy; most frequently diagnosed cancer of biliary tract ▪ High fatality rate due to typically late diagnosis ▪ Most gallbladder cancers arise within fundus ▪ May obstruct bile flow at common bile duct/ duodenum RISK FACTORS ▪ Chronic gallbladder inflammation ▪ ▪ ▪ ▪ ▪ ▫ Cholelithiasis (gallstones), primary sclerosing cholangitis, porcelain gallbladder, gallbladder polyps, biliary cysts; chronic infection (e.g. Salmonella typhi, Helicobacter bilis) More common in individuals who are biologically female Obesity Cigarette smoking Occupational exposure to carcinogens: textile, oil, paper, chemical industries, radon (mining) Genetic predisposition OSMOSIS.ORG 245

COMPLICATIONS ▪ Biliary fistula ▪ Local/nodal/distant metastases SIGNS & SYMPTOMS ▪ Often asymptomatic in early stages; malignancy discovered incidentally after symptoms mimic benign gallbladder disease ▪ Non-specific symptoms ▫ Malaise, pain, anorexia, nausea, vomiting, weight loss ▪ Clinical manifestations (when bile drainage obstructed) ▫ Jaundice, dark urine ▪ Palpable gallbladder DIAGNOSIS DIAGNOSTIC IMAGING EUS guided/percutaneous biopsy, CT scan, MRI, PET, MRCP ▪ Tumor visualization, histopathological analysis, grading, TNM staging, potential for resection LAB RESULTS ▪ Tumor markers: CA 19-9; CEA ▪ Liver function tests ▫ Consistent with biliary obstruction, cholestasis ▫ Elevated transaminases, gammaglutamyl transpeptidase, alkaline phosphatase ▫ Elevated bilirubin 246 OSMOSIS.ORG Figure 32.11 Histological appearance of gallbladder adenocarcinoma. The tumor cells show increased nuclear size, prominent nucleoli and are forming tubular structures. TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Simple/radical cholecystectomy OTHER INTERVENTIONS ▪ Radiation

Chapter 32 Gastrointestinal Cancers HEPATOBLASTOMA osms.it/hepatoblastoma PATHOLOGY & CAUSES ▪ Common primary childhood hepatic malignancy; arises from primitive hepatic cells ▪ Usually occurs in right lobe of liver ▪ Morphologically diverse tumor: composed of many cell types including embryonal hepatocytes, tissues (e.g. bone, striated muscle) ▪ Extramedullary hematopoiesis may occur in sinusoids ▪ Usually present during first two years of life DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound, percutaneous biopsy, CT scan with/without contrast, MRI ▪ Diagnostic workup for tumor visualization, histopathological analysis, grading, pretreatment staging system (PRETEXT); potential for resection LAB RESULTS ▪ Elevated alpha-fetoprotein (AFP) ▪ Genetic testing RISK FACTORS ▪ ▪ ▪ ▪ ▪ ▪ Beckwith Wiedemann syndrome Trisomies 18, 21 Familial adenomatous polyposis Type Ia glycogen storage disease Li–Fraumeni syndrome More common in individuals who are biologically male COMPLICATIONS ▪ Ectopic gonadotropin → precocious puberty (uncommon) ▪ Fatal hepatic hemorrhage, rupture ▪ Metastasis: commonly lungs Figure 32.12 Histological appearance of a hepatoblastoma, a tumor of immature hepatocytes. SIGNS & SYMPTOMS ▪ Children ▫ Abdominal mass; discomfort ▪ Anorexia, weight loss, precocious puberty TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Resection OSMOSIS.ORG 247

HEPATOCELLULAR CARCINOMA osms.it/hepatocellular-carcinoma PATHOLOGY & CAUSES ▪ Hepatic malignancy commonly diagnosed in presence of chronic liver disease RISK FACTORS ▪ Hepatitis B/C infection, coinfection with hepatitis D ▪ Hereditary hemochromatosis ▪ Cirrhosis ▪ Smoking; frequent alcohol consumption ▪ Obesity ▪ Alpha-1 antitrypsin deficiency ▪ Gallstones ▪ Chronic exposure to aflatoxin (mycotoxin found in peanuts, soybeans, corn) ▪ More common in individuals who are biologically male SIGNS & SYMPTOMS ▪ Often no symptoms aside from those of chronic liver disease ▪ Epigastric pain; appetite, weight loss ▪ Palpable abdominal mass; manifestations of decompensated cirrhosis (e.g. splenomegaly, ascites, jaundice); hepatic bruit COMPLICATIONS ▪ Paraneoplastic syndrome: watery diarrhea, hypoglycemia, hypercalcemia, erythrocytosis; cutaneous lesions (e.g. pemphigus foliaceus) ▪ Extrahepatic metastasis: commonly lymph nodes, lungs, adrenal gland MNEMONIC: ABC Hepatocellular carcinoma etiology Aflatoxins Hep B Cirrhosis Hepatocellular carcinoma features AFP increased: classic marker Bile-producing: DDx from cholangiocarcinoma Most Common primary liver tumor 248 OSMOSIS.ORG Figure 32.13 An abdominal CT scan in the axial plane demonstrating a massive hepatocellular carcinoma. DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound with biopsy, CT scan, MDCT, arteriography, portography, MRI ▪ Tumor visualization, histopathological analysis, grading, TNM staging, potential for resection MRI angiography ▪ 3D characterization of lesion, hepatic circulation

Chapter 32 Gastrointestinal Cancers LAB RESULTS ▪ Elevated aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase; hyperbilirubinemia; hypoalbuminemia ▪ Elevated alpha-fetoprotein (most common serum marker) Figure 32.14 Gross pathology of hepatocellular carcinoma. TREATMENT MEDICATIONS Figure 32.15 Histological appearance of a hepatocellular carcinima. The cells show high nuclear variation, thickened nuclear envelopes and occasional prominent nucleoli. The cells also have abundant eosinophilic cytoplasm. ▪ Chemotherapy ▪ Systemic molecularly targeted therapy; sorafenib, nivolumab SURGERY ▪ Partial hepatectomy ▪ Liver transplant OTHER INTERVENTIONS ▪ Radiofrequency ablation ▪ Percutaneous ablation with ethanol/acetic acid ▪ Transarterial chemoembolization ▪ Cryoablation ▪ Radiation therapy; stereotactic body radiation therapy OSMOSIS.ORG 249

ORAL CANCER osms.it/oral-cancer PATHOLOGY & CAUSES ▪ Oral cavity malignancy; arises from mucosal surfaces ▫ Lips, buccal mucosa, anterior tongue, mouth floor, hard palate, gingiva, retromolar trigone ▫ Most often: squamous cell carcinoma ▪ May arise from normal mucosa/ premalignant lesions (e.g. erythroplakia, leukoplakia); undergo malignant transformation COMPLICATIONS ▪ Surgical resection → airway, speech, mastication, cosmetic complications ▪ Metastasis SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ Asymptomatic initially Pain/burning sensation Lump/ulcer visualized, palpated Hard, fixed lymph nodes DIAGNOSIS RISK FACTORS ▪ Tobacco (esp. with alcohol) ▪ Alcohol ▪ Human papillomavirus (HPV) infection: oropharynx ▪ Periodontal disease ▪ Chronic oral candidiasis ▪ Betel quid chewing ▪ Immunosuppression ▪ Hepatitis C infection ▪ Genetic polymorphisms: cytochrome P450 1A1 (CYPIA 1); glutathione S-transferase mu 1 (GSTM1); alcohol dehydrogenase 3 genotype → oropharyngeal cancers ▪ More common in individuals who are biologically male DIAGNOSTIC IMAGING CT scan/MRI ▪ Local spread/location of additional primary tumors LAB RESULTS ▪ Fine needle biopsy; histopathological diagnosis OTHER DIAGNOSTICS ▪ Palpation and visualization ▫ Of mucous membranes, oral cavity, lymph nodes ▪ Flexible laryngoscopy ▫ Back of throat, vocal cords MNEMONIC: PATH LAB Oral cancer risks Plummer-vinson syndrome Alcohol Tobacco Human papilloma virus Leukoplakia Asbestos Bad oral hygiene TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Radiation 250 OSMOSIS.ORG

Chapter 32 Gastrointestinal Cancers PANCREATIC CANCER osms.it/pancreatic-carcinoma PATHOLOGY & CAUSES ▪ Highly lethal malignancy of exocrine pancreas ▪ Usually unresectable at presentation RISK FACTORS ▪ Chronic pancreatitis ▪ Malignant transformation of pancreatic intraductal papillary mucinous neoplasm (IPMN) ▪ Genetic mutations (e.g. BRCA-1, BRCA-2, ATM, PALB2, CDKN2A, MLH1) ▪ Smoking; obesity; sedentary lifestyle COMPLICATIONS ▪ Hypercoagulability with possible venous/ arterial thromboembolism ▪ Paraneoplastic manifestations ▫ Bullous pemphigoid; nodular fat necrosis (pancreatic panniculitis) ▪ Metastasis SIGNS & SYMPTOMS ▪ Recent onset of diabetes mellitus ▪ Clinical presentation ▫ Tumor location ▪ Pain ▫ Epigastric, abdominal, may radiate to the back, may worsen after eating/when lying down; asthenia: ▪ Physical weakness, loss of strength; anorexia, nausea; weight loss; jaundice, dark urine ▪ Hepatomegaly; right upper quadrant mass; Courvoisier’s sign (nontender, palpable gallbladder at right costal margin); cachexia; metastasis: left supraclavicular/periumbilical lymphadenopathy, ascites, abdominal mass DIAGNOSIS DIAGNOSTIC IMAGING Transabdominal ultrasound ▪ Detects degree of biliary tract dilation, obstruction ERCP ▪ Increased visibility of pancreaticobiliary tree MRCP ▪ Visualization of liver parenchyma, vascular structures Laparoscopy ▪ Determines resectability Abdominal CT scan; contrast-enhanced CT scan, EUS guided/percutaneous biopsy ▪ Tumor visualization, histopathological analysis, grading, TNM staging LAB RESULTS ▪ Tumor marker: CA 9-19 ▪ Hyperbilirubinemia (mostly conjugated); elevated alkaline phosphatase OTHER DIAGNOSITCS Cardiac catheterization ▪ Measure pressure in right side of heart TREATMENT MEDICATIONS ▪ Chemotherapy with/without chemoradiotherapy SURGERY ▪ Resection (e.g. pancreaticoduodenectomy) ▫ Only curative treatment OSMOSIS.ORG 251

Figure 32.16 Cytological preparation of a pancreatic fine needle aspirate which demonstrates pancreatic adenocarcinoma. The group on the left is the cancer, with large, pleomorphic nuclei, which overlap with one another. Contrast these with the smaller, regularly spaced pancreatic ductal epithelial cells on the right. Figure 32.17 Histological appearance of pancreatic adenocarcinoma. The tumor cells form acini, small sack like spaces surrounded by malignant glandular cells. STOMACH (GASTRIC) CANCER osms.it/stomach-cancer PATHOLOGY & CAUSES ▪ Aggressive adenocarcinoma arising from gastric mucosa TYPES Diffuse type (G-DIF): undifferentiated ▪ Impairment/lack of adhesion molecule E-cadherin ▪ Genetic mutation (germline, somatic, epigenetic methylation) of CDH1 gene → inactivation of CDH1 → nonfunctional E-cadherin → unregulated division (impaired tumor suppressor function); increased ability to spread, invade adjacent structures ▫ Autosomal dominant inheritance pattern ▫ More aggressive than G-INT Intestinal type (G-INT): well-differentiated ▪ Due to environmental factors; more 252 OSMOSIS.ORG common in high-risk populations ▪ Intercellular adhesion molecules → adherence of tumor cells → arrangement in glandular formations RISK FACTORS ▪ Primary cause (G-INT) ▫ H. pylori infection ▪ Family history of gastric cancer ▪ Autoimmune atrophic gastritis ▪ Lifestyle ▫ Smoking, alcohol consumption ▪ Diet ▫ Nitrates, nitrosamines, highly-salted foods; pickled/smoked foods ▪ Obesity ▪ Risk increases with age ▪ More common in individuals who are biologically male

Chapter 32 Gastrointestinal Cancers ▪ Protective factors ▫ Intake of fruit, vegetables, fiber, folate COMPLICATIONS ▪ Metastasis to liver, peritoneum, lymph nodes, etc. ▪ Paraneoplastic manifestations ▫ Seborrheic keratoses, polyarteritis nodosa, Trousseau’s syndrome (spontaneous, recurrent, migratory venous thrombosis) DIAGNOSIS DIAGNOSTIC IMAGING Esophagogastroduodenoscopy with biopsy, barium studies, abdominopelvic CT scan ▪ Tumor visualization, histopathological analysis, grading, TNM staging, potential for resection OTHER DIAGNOSTICS Physical examination ▪ Enlarged supraclavicular, anterior axillary, periumbilical lymph nodes ▪ Palpable abdominal mass Figure 32.18 Gross pathology of gastric carcinoma. The stomach has been pinned flat. The tumor is found in the antrum. SIGNS & SYMPTOMS ▪ Asymptomatic initially ▪ Early symptoms ▫ Vague constitutional symptoms (e.g. malaise, loss of appetite, dyspepsia) ▪ With disease progression ▫ Epigastric pain, nausea, vomiting, dysphagia, weight loss ▪ If GI bleeding ▫ Anemia, melena, coffee-ground hematemesis ▪ Pseudoachalasia syndrome (difficulty moving food, liquids from esophagus to stomach) ▫ If tumor extends to Auerbach’s plexus/obstruction occurs near gastroesophageal junction Figure 32.19 The histological appearance of a well-differentiated gastric adenocarcinoma of intestinal type. The tumor is composed of disordered glands, the cells of which have large, hyperchromatic nuclei. OSMOSIS.ORG 253

TREATMENT MEDICATIONS Chemotherapy ▪ G-INT, G-DIF differ in susceptibility to chemotherapeutic agents ▪ Eradication of H pylori infection SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Chemoradiotherapy WARTHIN'S TUMOR osms.it/warthins-tumor PATHOLOGY & CAUSES ▪ Uncommon benign tumor; arises from salivary gland ▪ AKA papillary cystadenoma lymphomatosum ▪ May involve submandibular/sublingual/ parotid gland (most common) ▪ Unilateral/bilateral, slow-growing RISK FACTORS ▪ Smoking ▪ Risk increases with age ▪ More common in individuals who are biologically male COMPLICATIONS ▪ Malignant transformation (rare) 254 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Development of painless nodular mass, usually near mandible angle DIAGNOSIS OTHER DIAGNOSTICS ▪ Easily palpable tumor Fine needle aspiration ▪ Histopathological diagnosis TREATMENT SURGERY ▪ Local resection/parotidectomy