245b neuroendocrine tumors

Question 1

neuroendocrine tumors - source? secrete anything? receptors? stain?

Answer 1

enterochromaffin cells

have granules that can secrete hormones and amines

functional (give syndrome) and non-functional

somatostatin receptors + other markers

chromogranin A (CgA) - monitor for treatment response

Question 2

pancreatic neuroendocrine tumors - what peptides can be produced?

Answer 2

glucagon, insulin, somatostatin, pancreatic polypeptide, serotonin + ecotpopic hormones

50% don’t product anything

Question 3

carcinoid syndrome (first aid)

Answer 3

Rare syndrome caused by carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT).

Not seen if tumor is limited to GI tract (5-HT undergoes first-pass metabolism in liver). Results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease.

increased 5-hydroxyindoleacetic acid (5-HIAA) in urine, niacin deficiency (pellagra).

Treatment: resection, somatostatin analog (octreotide)

rule of 1/ 3rds
1/3 metasize
1/3 present with 2nd malignnacy
1/3 are multiple

most common malignancy in small intestine

Question 4

when do most NET become symptomatic?

Answer 4

metastasis

Question 5

Zollinger-Ellison syndrome (first aid)

Answer 5

Gastrin-secreting tumor of pancreas or duodenum. Acid hypersecretion causes recurrent ulcers in distal duodenum and jejunum.

Presents with abdominal pain (peptic ulcer disease, distal ulcers), diarrhea (malabsorption). May be associated with MEN 1.

Question 6

Insulinoma (first aid)

Answer 6

Tumor of “ cells of pancreas –> overproduction of insulin –> hypoglycemia.

Whipple triad of episodic CNS symptoms: lethargy, syncope, and diplopia.

Symptomatic patients have decreased blood glucose and increased C-peptide levels (vs. exogenous insulin use).

Treatment: surgical resection.

Question 7

imaging studies with NETs

Answer 7

somatostatin-receptor –> octreoscan

Question 8

somatostatin - function? drug use? drug?

Answer 8

bioactive neuropeptide –> inhibitors effects throughout body including GI tract –> blocks gastric acid, amylase; anti-inhibitory

ocretoride prolongs life

drug is octreotide (longer half life)

Question 9

somatostatin receptors - type of receptors? functions?

Answer 9

5 subtypes

GPCR

antisecretory, antiproliferative, apoptotic effects

Question 10

mTOR - role? drug? cancer rx?

Answer 10

central role in proliferation pathways in cancers to include cell growth, angiogenesis, protein synthesis

downstream of signaling that is deregulated in cancer so good target

drug: everolimus –I mTOR

good for insulinoma and NETs

Question 11

VEGF function? drug?

Answer 11

angiogenesis - NETs express VEGF for vessel growth

Bevacizumab –I VEGF