Pancreas is the common site for neuroendcrine tumours. Insulinomas, gastrinomas and non-functional neuroendocrine tumours are three common btypes may occur in pancreas. NET may be multifocal, malignant and part of MEN syndrome, making prognosis poor.

1. Pancreatic Neuroendocrine Tumours (NETs)

2. TUMOUR INCIDENCE PRESENTATION MALIGN (%)
INSULINOMA (beta C) 70-80 Weakness, Sweating, Tremor, Tachycardia,
anxiety, fatigue, dizziness, disorientation, seizures
<10
GASTRINOMA 20-25 Intractable peptic ulcer, diarhoea 60-80
NON FUNCTIONAL
TUMOURS
30-50 Weight loss, fatigue,epigastric discomfort,
obstructive jaundice, duodenal obstruction
60-90
VIPoma 4 Profuse watery diarrhoea, Hypokalaemia,
hypotension, abdominal pain
80
GUCAGANOMA (alpha C) 4 Diabetes, severe weight loss, diarrhoea, glossitis,
Migratory necrolytic skin rash
80
SOMATISTATINOMA (delta C) <5 Diarrhoea, Neurofifromatosis, Cholelithiasis 50
CARCINOID <1 Flushing, Sweating, Diarrhoea 90
ACTHoma <1 Cushing’s Syndrome >90
GRFoma <1 Acromegaly 30
Multiple Endocrine Neoplasia type 1 (MEN1) syndrome is a risk factor for pancreatic NETs

3. • First described by Hariss 1924
• Commonest hormone producing NET of GIT
• 99% Pancreatic Origin
• 90% Solitary, 90% <2cm, 90% Benign
• 10% associated with MEN 1 (Multiple, Malignant 25%)
• Median age of Presentation 47years.
• Female : Male ratio 1.4 : 1
INSULINOMA

4. INSULINOMA
HYPOGLYCAEMIA
• GLUCAGON
• CATECHOLAMINE (sweating, weakness, tremor, nausea,
palpitation, anxiety)
• CORTISOL
• GH
Whipple’s Triad
1. Hypoglycaemia after fasting or exercise
2. Blood Glucose level <2.8 mmol/L(70mg%)
3. Relief of symptoms on IV admn. Of Glucose
Episodic
1. Diplopia
2. Blurred vision
3. Confusion
4. Amnesia
5. Abnormal behaviour
6. Convulsion
Neuroglucopenic symptoms

5. Estimation of
• Insulin
• Proinsulin
• C-Peptide
• Blood Glucose
BIOCHEMICAL DIAGNOSIS
LOCALIZATION STUDIES
Imaging Studies
• EUS (Endoscopic Ultrasound)
• CT Scan
• Abdominal Ultrasound
• MRI Scan
• IOUS (Intraoperative Ultrasound)
• Somatostatin Receptor Studies

6. MANAGEMENT
SURGICAL
• Enucleation
• Distal Pancreatectomy
• Whipple’s Procedure in a few
Blind resection should not be performed
MEDICAL
• Diazoxide (success 50%)
• Streptozotocin & Doxorubicin
For unresectable metastatic
disease & when Surgery is
not feasible
ABLATIVE SURGERY FOR METASTATIC DISEASE
• Hepatic artery embolization
• Chemoembolization
• RF Ablation
• Radiation

7. GASTRINOMA (ZOLLINGER- ELLISON SYNDROME)
• Mean Age 50 years
• Male : Female + 3:2
• MEN 1 in approximately 25% of cases (MENI – Parathyroid+Pancreas+pituitary)
• Sporadic 75-80%
• Sites other than Pancreas – Duodenum, Stomach antrum, Ovary, Lung & Heart
• Malignant >60% at time of diagnosis
GASTRINOMA TRIANGLE

8. LOCATIONS OF PEPTIC ULCERS IN Z-E SYNDROME

9. SYMPTOMS IN Z-E SYNDROME

10. SUSPICION FOR Z-E SYNDROME
1.Refractory Peptic Ulcer Disease(PUD) in the
absence of Helicobacter Pylorie
2.PUD in association with chronic diarrhoea
3.Post - bulbar duodenal ulcer.
4.Multiple duodenal, jejunal and oesophageal ulcers
5.PUD with giant ulcers

11. DIAGNOSIS OF Z – E SYNDROME
• GASTRIC pH IS BELOW 2.5
• SERUM GASTRIN ABOVE 1000rg/ml (N -100pg/ml)
• SECRETIN TEST – increase in serum gastrin of > 200pg/ml

12. MANAGEMENT OF Z – E SYNDROME
1. In one third of cases the result of conventional imaging studies are negative
2. Pancreatic gastrinomas are often larger than 1cm. In diameter and that of duodenum usually smaller.
3. Even if a tumour is found in pancreas, duodenectomy is recommended to detect additional tumour
if the patient has MEN 1
4. In metastatic gastrinomas – Streptozocin with 5-FU or Doxorubicin.
(PPI, Octreotide)

13. PROGNOSIS AND PREDICTIVE FACTORS
• Progress is relatively slow 5 yr survival is 65% and 10yr survival is 51%
• Complete tumour excision can give can give 10yr survival 90-100%
• Patients with pancreatic Gastrinomas have the worth prognosis than
those in the duodenum.
• No marker to predict the biological behaviour of gastrinoma.

14. Pancreatic Neuroendocrine Tumors (NETs)
(1) BENIGN
(2) MALIGNANT
Pancreatic Neuroendocrine Tumors (NETs)
(1) FUNCTIONAL
(2) NON FUNCTIONAL
Most non-functional tumours are malignant

15. NON – FUNCTIONAL PANCREATIC ENDOCRINE TUMOURS
NF-PETs
• Accounts for 30-50% of all PETs
• Incidence in 50-60yrs of age
• Distributed throughout pancreas Head : Body : Tail - 7:1:1.5
• Size usually >5cm when diagnosed, unifocal except in MEN 1
• Though non-functional yet express hormones e.g. gastrin, insulin on
immunohistochemistry. Stains positive for Chromogranin and
synaptophysin

16. NON – FUNCTIONAL PANCREATIC ENDOCRINE TUMOURS
NF-PETs
• About 70% of all NF-PETs are malignant.
• Usually present Late
• Presenting symptoms non hormonal but due to SOL and malignant spread
(Epigastric mass, Pain, Jaundice, anorexia, Weight loss, pancreatitis)
• Metastasis in liver is often the first presentation.
• Prognosis relatively poorer than functional PETs
• Overall 5yr survival is 65%

17. DIAGNOSIS - NF-PETs
• Increased level of serum Chromogranin A (in 50-80% of cases)
• Imaging studies to identify the primary lesion and for metastasis
• Hyper-density and Calcification in CT scan differentiate it from exocrine
pancreatic adenocarcinoma
• Somatostatin receptor scintigraphy (SRS)
• Resectability, long term survival and prognosis is relatively better than the
adenocarcinoma.
• Curative resection is possible in about 65% cases

18. SURGERY FOR PANCREATIC ENDOCRINE TUMOURS
• Enucleation
• Pancreatoduodenectomy
• Distal pancreatectomy:
• Total gastrectomy
• Parietal cell vagotomy
• Liver resection
• Radiofrequency ablation
• Cryosurgical ablation

19. FMTC
(Familial Medullary Thyroid Ca)
MEN 2A
1. MTC
2. pHPT
3. B/L Pheochromocytoma
MEN 2B
1. MTC
2. B/L Pheochromocytomas
3. Facial & Mucosal Neurinomas
Intestinal ganglioneuromas, Marfanoid
features
MEN 2
PARATHYROID
PANCREAS
PITUITARY
MEN 1
MULTIPLE ENDOCRINE NEOPLASM (MEN)
pHPT is the
first manifestation
In MEN 1 PETs
Multifocal Gastrinomas
Is common
In MEN 1 Pituitary
Prolactinoma is
commoner
Caused by mutation of RET proto-oncogene
Medullary Thyroid cancer (MTC) is common in all the three types
Calcitonin high in all the cases
MTC is most aggressive in MEN 2B

20. Thank you