Gastric Cancers and Gastrinomas Flashcards by Karina Katchko

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

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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

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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

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Type 1 GI neuroendocrine tumor tx

endoscopic resection 2cm

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What is another name for GI neuroendocrine tumors?

Carcinoid tumors

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Type 2 GI neuroendocrine tumor features

associated w/gastrinomas/MEN1
high gastrin levels
typically indolent

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What is MEN1?

AD predisposition to tumors of the parathyroid, pituitary and enteropancreatic cells

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Type 2 GI neuroendocrine tumor tx

endoscopic resection <2cm

address gastrinoma

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Type 3 GI neuroendocrine tumor features

sporadic, most aggressive
hepatic or local meastases
normal serum gastrin

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Type 3 GI neuroendocrine tumor tx

partial or total gastrectomy w/local lymph node resection

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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

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Gastrinoma features

sporadic
men
assoc w/MEN1 (parathyroid and pituitary adenomas)
20-50 yos

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Where do gastrinomas usually arise from?

duodenum

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What are the differences between duodenal and pancreatic gastrinomas?

D-small, often multiple

P-solitary, more malignant potential

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Presentation for gastrinoma?

PUD
acid reflux
prominent gastric folds
diarrhea

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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)

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What is the secretin stimulation test?

secretin stimulates the release of gastrin by gastrinoma cells, inhibits gastrin release by normal gastric G cells

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What is the calcium infusion study: arterial calcium gluconate infusion?

positive study-increased serum gastrin and calcium levels

to dx gastrinoma

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Tx for gastrinoma?

high dose acid suppression
surgery
metastatic disease-somastostatin analogs, liver directed therapy, chemo

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Do gastrinoma patients with MEN1 have a better or worse prognosis?

lower rate of metastasis and higher survival

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What is associated with gastrinoma that confers a worse prognosis?

higher fasting gastrin level

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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