HReviewCarcinoid and Pancreatic Neuroendocrine Tumors Flashcards
(18 cards)
NET
Neuroendocrine tumors
Secrete peptides
1-2 per 100000
prevalence > 100000 in US
Histologic classifications
Well differentiated
Poorly differentiated
- Grade / mitotic count / Ki67 index / ENETs, Who
Well differentiated
- Grade / mitotic count / Ki67 index / ENETs, Who
- G1-G2 / < 20 per 10 HPF / < 20% ki67 / Grade 1-2
Poorly differentiated
- Grade / mitotic count / Ki67 index / ENETs, Who
- G3 / > 20 per 10 HPF / > 20% ki67 / Grade 3 small/large cell
Survival 5 years in %
- G1 : 95
- G2: 73
- G3: 27
NET classifications
According to site of origin
- Carcinoid Tumors
- Pancreatic neuroendocrine tumors (islet cell tum ors)
Pancreatic NET
30-40% with hormone hypersecretion
- Gastronoma
- Insulinoma
- Glucagonoma
- VIP
- PTHrp
60-70% non functioning
Managment of secretory symptoms
- Insulinoma
- Glucagonoma
- VIPoma
- Gastrinoma
-
Insulinoma
- Diet modifications
- Diazoxide
- potassium channelactivator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. This switches off voltage-gated calcium ion channels which inhibits the generation of an action potential
- evelolimus
- +/- somatostatin analog
-
Glucagonoma
- Somatostatin analog
- TPN
-
VIPoma
- Somatostatin Analog
-
Gastrinoma
- PPIs
- somatostatin analog
Pancreatic NET : Surgical resection
Enucleation, Distal pancreatectomy or whipple
MEN-I multiple cancers
Prognosis good with complete resecction
Carcinoids tumors
**Foregut 33% **
- lungs bronchi, stomach
**Mid gut 34% **
- small intestine / bowel, appendix
Hindgut 14%
Distal large bowel, rectum
Bronchial carcinoid
Cough, wheezing and hemoptysis
Ectopic ACTH (MC) cushing syndrome
Atypical do much worse 30-40% survival
Gastric carcinoid tumors
3 types
- **Type I : **
- associated with atrophic gastritis Type A
-
Type II:
- Associated with zollinger ellison syndrome MEN I
-
Type III:
- Sporadic gastric carcinoids
Type I and II carcinoids are associated with hypergastrinemia
- Enterochromaffin like Cell -> ECL cell hyperplasia -> Multiple gastric carcinoids
Sporatic Gastric carcinoids
15-20%
Solitary usually > 1 cm and invasie with mets usually
Appendiceal carcinoids
Rectal
if > 2 cm will need octreoscan (for staging) right colectomy
< 2 can have just a simple appendectomy
Rectal carcinoid > 2 cm octreoscan with staging and proper treatment
< 2 local excision
Carcinoid syndrome
Tx: meds / Liver focused
Mainly serotonin and other neuropeptides
Flushing, diarrhea and eventual right sided valvular heart dz
Carcinoid syndrome
Tx: meds / Liver focused
- Somatostatins (octereotide /octereotide LAR mothly)
- Interferon a
- Chemo - Streptozocin/5FU vs Doxorubicin/5FU
- Liver directed therapy: Hepatic artery embolization
- Liver transplantation (but dz recurrence is common)
Pancreatic NET tx:
Pancreatic NET :
Streptozocin based therapy showed promic but not used as much
Temozolomide based therapy better promises
Neuroendocrine tumor and pathways
RTK:
PI3-K:
AKT:
mTOR:
RTK: Receptor Tyrosin Kinase
PI3-K: Phosphoinositide 3-kinase
AKT: Protein Kinase B
mTOR: Mammalian target of rapamycin
PI3K activation activates AKT which activates mTOR.
- these pathway is an intracellular signalling pathway important in apoptosis and hence cancer
Drugs:
- Bevacizumab
- Sunitinib
- Sorafenib
- Pazopnib
- Everolimus
- Temsirolimus
Growth factors:
-
VEGF: Vascular endothelial growth factor
- Bevacizumab
Growthfactor Receptors:
- PDGFR: Platelet-derived growth factor Rec
- VEGFR: Vascular endothelial growth factor Rec.
-
RET (MEN2)
- Sunitinib
- sorfenib
- pazopanib
PI3-K
AKT
(TSC 1 & 2: Tuberous sclerosis protien)
mTOR
- Everolimus
- Temsirolimus
So what does all this mean
Meds
- Somatostatin analogs
- Hepatic directed therapies
- Alkylating agents
- VEGF pathway (sunitinib) and mTOR inhibitor(Everolimus)
-
Somatostatin analogs
- Symptoms (and in carcinoid for tumor) control
- Hepatic directed therapies
- Hepatic predominant dz
- Alkylating agents
- (Streptozocin or temozolomide) are active in pancreatic NET/ not much with carcinoid dz
- VEGF pathway (sunitinib) and mTOR inhibitor(Everolimus)
- Improve progression free survival in advance pancreatic NET
Carcinoid syndrome
Flushing: The most important clinical finding is flushingof the skin, usually of the head and the upper part of thorax.[4] Secretory diarrhea and abdominal cramps are also characteristic features of the syndrome.
Diarrhea: When the diarrhea is intensive it may lead toelectrolyte disturbance and dehydration. Other associated symptoms are nausea, and vomiting.Bronchoconstriction, which may be histamine-induced, affects a smaller number of patients and often accompanies flushing.
Secondary restrictive cardiomyopathy: About 50% of patients have cardiac abnormalities classically of the restrictive-type caused by serotonin-induced fibrosis of the valvular endocardium, notably the tricuspid and pulmonary valves, called cardiac fibrosis. This results in a heart with normal rhythm and contractility, but reduced preload and end-diastolic volume. “TIPS” is an acronym forTricuspid Insufficiency, Pulmonary Stenosis (fibrosis of tricuspid and pulmonary valves).[citation needed]
Abdominal pain: Due to desmoplastic reaction of the mesentery or hepatic metastases.[citation needed]
