Gastric Cancers and Gastrinomas Flashcards
Key features of general gastrointestinal neuroendocrine tumors types
well differentiated-solid, trabecular, gyriform or glandular pattern, salt and pepper chromatin, granular cytoplasm
poorly differentiated-resembled small or large cell neuroendocrine lung carcinoma
What is a marker for GI neuroendocrine tumors?
Ki67-large protein involved in cell cycle regulation and/or organization of the nucleolus
increased staining-worse prognosis
Type 1 GI neuroendocrine tumor features
derived from ECL cells associated w/chronic atrophic gastritis and pernicious anemia women old small and multiple high gastrin, turns to carcinoid tumors usually indolent and benign
Type 1 GI neuroendocrine tumor tx
endoscopic resection 2cm
What is another name for GI neuroendocrine tumors?
Carcinoid tumors
Type 2 GI neuroendocrine tumor features
associated w/gastrinomas/MEN1
high gastrin levels
typically indolent
What is MEN1?
AD predisposition to tumors of the parathyroid, pituitary and enteropancreatic cells
Type 2 GI neuroendocrine tumor tx
endoscopic resection <2cm
address gastrinoma
Type 3 GI neuroendocrine tumor features
sporadic, most aggressive
hepatic or local meastases
normal serum gastrin
Type 3 GI neuroendocrine tumor tx
partial or total gastrectomy w/local lymph node resection
What is a gastrinoma? Alias?
Zollinger-Ellison syndrome
hypersecretion of gastric acid due to ecess gastrin
derived from ECL cells, a neuroendocrine tumor
designated by clinical production of gastrin, NOT morphologic appearance/gastrin staining
Gastrinoma features
sporadic
men
assoc w/MEN1 (parathyroid and pituitary adenomas)
20-50 yos
Where do gastrinomas usually arise from?
duodenum
What are the differences between duodenal and pancreatic gastrinomas?
D-small, often multiple
P-solitary, more malignant potential
Presentation for gastrinoma?
PUD
acid reflux
prominent gastric folds
diarrhea
How do you diagnose gastrinoma?
fasting serum gastrin secretin stimulation test calcium infusion study:arterial calcium gluconate infusion CT MRI Octreoscan US (most sensitive imaging modality)
What is the secretin stimulation test?
secretin stimulates the release of gastrin by gastrinoma cells, inhibits gastrin release by normal gastric G cells
What is the calcium infusion study: arterial calcium gluconate infusion?
positive study-increased serum gastrin and calcium levels
to dx gastrinoma
Tx for gastrinoma?
high dose acid suppression
surgery
metastatic disease-somastostatin analogs, liver directed therapy, chemo
Do gastrinoma patients with MEN1 have a better or worse prognosis?
lower rate of metastasis and higher survival
What is associated with gastrinoma that confers a worse prognosis?
higher fasting gastrin level
Where is gastric adenocarcinoma more common?
developing countries
higher geographic latitudes
What is happening to the frequency of gastric adenocarcinoma?
rapid decline overall
increased incidence of proximal gastric cancers that are more aggressive and not associated w/atrophy and intestinal metaplasia
What are the 2 subtypes of adenocarcinoma?
Intestinal-sporadic, env. factors, males, older
Diffuse-no sex predominance, younger, wrose prognosis
What are some environmental risk factors for gastric adenocarcinoma?
salt, nitroso compounds, obesity, smoking, Hpylori, EPV, type A blood
What physical risk factors for gastric adenocarcinoma?
gastric ulcers gastric surgery (billroth II> billroth I)
What are other risk factors for gastric adenocarcinoma?
pernicious anemia gastric adenomatous polyps immunodeficiency syndromes menetrier's disease genetic causes (HDGC, FAP, HNPCC, Peutz-Jegher's, Li-Fraumeni)
What are gastric adenocarcinoma protective factors?
fruits/veggies, fiber
NSAIDs???
Female reproductive hormones
Key features of intestinal gastric adenocarcinoma
related to h. pylori–>reactive nitric oxides induce DNA abnormalities, ie on bet-catenin–>Wnt pathway activation–>activation of bet catinin/Tcell factor complex–>genes that stimulate proliferation, angiogenesis, tumor invasion and metastasis
List the ways that NO can lead to cancer
causes oxidative DNA damage angiogenesis inhibition of DNA repair enzymes Dysregulation of apoptosis oncogene expression modulation of transcription factors
What genes are invovled in intestinal gastric adenocarcinoma?
alterations in tumor suppressor genes
What additional site can cells leading to intestinal gastric adenocarcinoma arise from?
bone marrow
What is the sequence leading to gastric adenocarcinoma?
non-atrophic gastritis-> atrophic gastritis->intestinal metaplasia->dysplasia->maligancy
List the variants of intestinal gastric adenocarcinoma
mucinous, tubular, papillary, adenosquamous histologic variants
Where is intestinal gastric adenocarcinoma usually located?
incisura, antrum or body
What genetic markers are common in diffuse gastric adenocarcinoma?
E cadherin (CDH1 gene, 16q22.1) defective loss of expression leads to defective intercellular adhesions
What does E cadherin do?
cell adhesion, transmitting signals, controlling cell movement, tumor suppressor gene, regulating activity of other genes
What histologic finding is seen with diffuse gastric adenocarcinoma?
signet ring histology
Is H pylori associated with diffuse gastric adenocarcinoma?
yes
What is the clinical presentation for gastric adenocarcinoma?
wt loss abd pain dysphagia GI bleed early satiety & nausea w/linitis plastica (aggressive form of diffuse type gastric adenocarcinoma) ulcer, mass
What is the treatment for gastric adenocarcinoma?
surgery (curative)
adjuvant/neoadjuvant chemo
radiation for unresectable disease
endoscopic methods
What is Hereditary diffuse cancer?
AD w/high penetrance
avg age of onset 38
>80% lifetime cumulative risk for advanced gastric cancer by age 80
What other cancer is HDGC associated with?
breast cancer
How do you manage HDGC?
prophylactic gastrectomy after age 20
random biopsy surviellance
breast cancer screening
What is gastric lymphoma?
most common extranodal site of lymphoma
50s-60s
males
non-hodgkin lymphomas most often
ARe primary or secondary NHLs/gastric lymphomas more common?
secondary, primary is very rare
What are risk factors for gastric lymphoma?
H pylori infection-MALT lymphoma
Immunodeficiency and immunosuppression
celiac disease-EATL & Bcell lymphoma
autoimmune diseases (linked to immunosuppressive therapy)
What are the most common primary gastric lymphoma NHLs?
MALT lymphoma
DLBCL
What is the clinical presentation for gastric lymphoma?
Epigastric pain anorexia wt loss nausea/vomiting occult bleeding B symptoms
What is seen on EGD of gastric lympohoma?
SUBTLE
erythema, mass, ulcer, nodularity, thickened gastric folds
Features of gastric ESCC (extrapulmonary small cell lung cancer)
rare males 70yo usually locally advanced/disseminated on rpesentation 8% 2r survival
What are the symptoms of gastric ESCC?
mass
ulceration
bleeding
invasion into adjacent structures
Where is gastric ESCC usually located?
upper third of stomach
What is the treatment for gastric ESCC?
surgery for debulking nd chemo