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

17. Glucagonoma: raised serum pancreatic glucagon
and enteroglucagon
VIPoma: raised fasting vasoactive intestinal peptide
Somatostatinoma: elevated fasting somatostatin
All NETs: elevated chromogranin A

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.

21. 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

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