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GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS
1. DR FARHAN ALI
MBBS,MCPS,FCPS
MEDICAL SPECIALIST
CDA HOSPITAL ISLAMABAD
PAKISTAN
2. BACKGROUND
1969 (Pearse) described APUD cells (amine precursor
uptake and decarboxylation) cells that make polypeptides
and biogenic amines
These cells have dense core secretory granules which
store and release hormones in response to external
stimuli
3. Do not have axons/synapses
Are part of the diffuse endocrine system (DES)
Endocrine tumors of the gut and pancreas originate from
DES cells
4. Incidence
Incidence 1-2 in 100,000
Account for <2% of GI malignancies
Neuroendocrine tumors of the lung, GI tract and
mediastinum have a higher incidence in patients
>50
carcinoid of the appendix have a higher incidence
in patients age <30
5. WHO CLASSIFICATION
Well differentiated NET (non-invasive, benign
behaving or uncertain malignant potential)
Well-differentiated NE carcinomas (low grade
malignant and has invasion or muscularis propria or
metastasis)
Poorly differentiated endocrine carcinomas (high grade,
malignant)
6. GENERAL CLASSIFICATION
1- Carcinoid Tumors
25% foregut (lung, thymus, gastric mucosa,
duodenum)
40-60% midgut (distal ileum and jejunum) (includes
carcinoid syndrome)
Hindgut (colon, rectum)
2-Endocrine Pancreatic Tumors
60% Functioning (Zollinger Ellison, insulinoma,
glucagonomas, VIPomas, etc)
Non-functioning (usually large and metastatic at the
time of diagnosis
7. 1-Endocrine Pancreatic Tumors
a-INSULINOMAS
Islet cell tumors
Secrete excess of predominantly insulin
Usually present at age 40-50
More common in women
Clinical symptoms include sweating, tremors,
tachycardia, confusion, weakness
10% of patients develop metastasis
Complete resection cures most patients
8. b-GASTRINOMAS
Over secretion of gastrin
Zollinger-Ellison Syndrome: atypical peptic ulcer
disease, gastric hyperacidity and hypersecretion,
associated with islet cell pancreatic tumors
Age at diagnosis ~50
More common in males (~60%)
Metastasis in 60% of patients
Complete resection results in 10 year survival of
90%; less likely if large primary
9. c-GLUCAGONOMAS
Presents with mild DM and severe dermatitis
(necrolytic migratory erythema), stomatitis, diarrhea
~70% are malignant
Metastasis in >60% patients
10. d-VIPOMAS
Over secretion of VIP
Causes watery diarrhea, marked hypokalemia
80% are associated with the pancreas
Metastasis occurs in ~70% of patients
Complete resection results in 5 year survival of 95%
11. e-SOMATOSTATINOMAS
Cholelithiasis, DM, diarrhea, weight loss, steatorrhea
Metastasis in ~50% patients
Complete resection with 5 year survival of 95% and if
has metastasis the 5 year survival decreases to 60%
12. 2-Carcinoid Tumours
arise in the thymus, bronchi and throughout the
gastrointestinal tract,
most commonly observed in the small bowel.
present due to local mass effects, e.g. small bowel
obstruction, appendicitis, pain from hepatic
metastases, or because of symptoms related to
hormone excess.
This includes ectopic secretion of ACTH, causing
Cushing's syndrome , or 5-HT, causing 'carcinoid
syndrome'.
13. CLINICAL FEATURES OF THE
CARCINOID SYNDROME
Flushing
Wheezing
Diarrhoea
Facial telangiectasia
Cardiac involvement (tricuspid regurgitation,
pulmonary stenosis, right ventricular endocardial
plaques leading to heart failure
14. Carcinoid syndrome only occurs when the
vasoactive hormones reach the systemic circulation.
In the case of gastrointestinal carcinoids, this
invariably means that the tumour has metastasised to
the liver, as hormones secreted by the primary
tumour into the portal vein are metabolised by the
liver
15. DIAGNOSTIC PROCEDURE
Biopsy Immunohistochemistry
Antibodies to chromogranin A
Neuron specific enolase
Stain for serotonin if suspect carcinoid
Stain for gastrin if suspect Zollinger – Ellison
16. LABORATORY EVALUATION
Carcinoid: 24 hour urinary 5-HIAA raised in
carcinoid tumors of the foregut and midgut but not
generally raised in tumors of the hindgut
Gastrinoma: raised basal serum gastrin, high gastric
acid secretion
Insulinoma: raised fasting insulin/glucose ratio,
proinsulin or C-peptide
18. RADIOLOGIC DIAGNOSIS
CT
MRI
US
Somatostatin Receptor Scintigraphy (SRS) –
based on presence of somatostatin receptors in
80-90% of NET
PET to evaluate tumor metastasis
Endoscopic ultrasound – sensitivity/specificity
appx 80% for tumors in pancreas and duodenum
and can allow for FNA
19. Anatomic Imaging: CT
Std Arterial
Venous Delayed
Imaging studies property of James Yao, MD. CT: computed tomography.
20. MRI = magnetic resonance imaging
Imaging studies property of James Yao, MD.
22. THERAPY
Surgery
For localized disease
Only way to cure
Can include debulking or laser procedures
however not applicable to all cases as many pts present with
metastatic disease
Medical therapy:
Somatostatin analogs
Interferon alpha
Diazoxide may reduce insulin secretion in insulinomas
Cytotoxic drugs
23. SOMATOSTATIN ANALOGS
Used since 1980’s
Hormone blocking agents that are synthetic
somatostatin derivatives (ex: octreotide and
lanreotide)
First line of treatment for neuroendocrine
gastroenteropancreatic tumors
2nd -3rd line for insulinomas and gastrinomas
Side effects: development of gallstones secondary
to inhibition of cholecystokinin release, pain at
site, hypo or hyperglycemia, rash, alopecia, fluid
retention
24.
25. Interferon Alpha
For mid-gut carcinoids
Work by direct effect on tumor cells by blocking cell
cycle in G1/S phase and inhibiting protein/hormone
synthesis and inhibition of angiogenic function
Can by used with or without somatostatin analogs
SE: flu-like symptoms, fever, anemia,
thrombocytopenia, leukopenia
26. CHEMOTHERAPY
Cytotoxic treatment is generally a palliative option for
metastasizing neuroendocrine carcinomas
Streptozotocin, + 5-FU and doxorubicin (response
rate >50% in malignant NET)
Cisplatin/paraplatin + etoposide (for poorly
differentiated NET in fore-gut