Name the endocrine tumors of pancreas and its management

1. Name the Endocrine Tumors of Pancreas
Describe investigations and treatment of
Insulinoma
Moderator : Prof Dr Vijay Arora
Presenter: Dr Ravi bhushan
SIR GANGARAM HOSPITAL NEW DELHI

2. PANCREAS

3. Physiology
The pancreas is divided functionally into
 Exocrine Pancreas
 85% of pancreatic mass
 Endocrine Pancreas
 2% of pancreatic mass

4. Exocrine Pancreas
• secretes a clear, alkaline (pH 7-8.3) solution of 1-2 L/day, containing
digestive enzymes
• secretion is stimulated by
 secretin
 CCK
 parasympathetic vagal discharge

5. Endocrine Pancreas
• Nearly one million islets of Langerhans in the normal adult
pancreas
• Vary greatly in size
• Larger islets are located closer to the major arterioles
• Smaller islets are embedded more deeply in the pancreatic
parenchyma
• Islet cells originate from neural crest cells, aka APUD cells

6. Components of Pancreatic islet

7. CELL
TYPE
% ISLET
CELLS
Location
within
islet
Distribution Hormones
secreted
Associated
tumor
syndrome
Diag
hormone
leve;s
Alpha 10% Peripheral Evenly distributed Glucagon(
glicentin,
TRH,CCK,
endorphin, PP,
Pancreastatin)
Glucagonoma;
Necrolytic
migratory
erythema, DM,
Hypoaminoacid
emia
Fasting>1000pg/
ml
Beta 70% Central Body/tail Insulin(TRH,
amylin,
Pancreastatin,
Prolactin)
Insulinoma;
Hypoglycemia
and associated
symptoms
>5microU/ml in
hypoglycemia
Delta 5% Evenly Evenly distributed Somatostatin Somatostatinom
a; DM,
Gallstones ,
Steatorrhoea
>160pg/ml

8. CELL
TYPE
% ISLET
CELLS
Location
within
islet
Distribution Hormone
ssecreted
Associated
tumor
syndrome
Diag
hormone
levels
D2 5% Evenly Evenly distributed VIP VIPoma; high
volume secretory
diarrhoea
hypokalemia.
Metab acidosis,
hypochlorhydria
Normal
<200pg/ml
F 15% Peripheral Head /uncinate PP -none
EC <1% Evenly Evenly distributed Substance P,
Serotonin
None
G Not present in
normal
physiological
state
NA Head, Uncinate
process,
Duodenum
Gastrin, ACTH
related
peptides
Gastrinoma,
Acid
hypersecretion,
Gastric ,
duodenal ulcers,
Diarrhoea
Suspicious
> 1000pg/ml

9. Pancreatic Endocrine Tumors
• Pancreatic endocrine tumors are rare approximately 5 per 1,000,000 per year
• Occurs at younger age
• Multifocal disease
• Some associated syndromes are
MEN 1 ,VHL ,NF

10. Pancreatic Endocrine Tumors
Functional Non Functional
MalignantBenign Benign Malignant
The histologic characteristics do not predict their clinical behavior
For all types of endocrine tumors, malignancy is defined by the presence of metastases

11. Insulinoma
• Most common functional tumor (60%)
• Av age : 45 yrs
• M=F

12. Insulinoma
• Originate from Beta cells of pancreas
• Almost universally in Pancreas
• Equal distribution in head body and tail.
• 90% are < 2 cm in size
• 90% are benign and solitary
• 90% are sporadic
• 10% associated with MEN1 syndrome

13. Clinical features:
• WHIPPLE’S TRIAD:
• Symptomatic Fasting hypoglycaemia
• Documented serum Glucose level <50 mg/dl
• Relief of symptoms with glucose intake
May present with syncopal attacks or Palpitation, Headache , Diaphoresis,
Confusion/Obtundation, Seizure.
Family members may report personality change.

14. Clinical features:
• Worse in mornings
• Weight gain

15. Investigations
Low Blood sugar level
High serum insulin level
High C-peptide level
Gold Standard test: 72hrs fasting test
 Neuroglycopenic symptoms
 Serum glucose<45mg/dl
 Serum level of insulin >5μU/L
 Serum C-peptide(>0.7ng.ml),Proinsulin >6.5 pmol

16. Investigations
Localization
CT and MRI for larger tumors
• EUS can detect small tumors (<2 cm in size) angiography showing a
“blush”
• EUS combined with Intra-op USG can detect almost all tumors.
• Portal Venous sampling for insulin level can detect 80% tumors
• Tumors have Somatostatin receptors(STR) , can be detected by
radiolabelled octreotide scan

17. Management
Preoperative management
• Optimization of hypoglycemia - slowly absorbable forms of
carbohydrates (e.g. starches, bread, potatoes, rice) generally are
preferred.
 Administration of diazoxide to prevent hypoglycemic attacks
• Other agents as verapamil, glucocorticoids, and growth hormone

18. Management
• Surgical resection - the only curative treatment for pancreatic
neuroendocrine neoplasms
• Management is similar for functional and non functional tumors
• Simple enucleation If small(< 2 cm) and away from pancreatic duct
• If Tumor is > 2cm and close to main pancreatic duct- Distal
pancreatectomy or pancraticoduodenectomy
• If tumor in head of pancreas: Pancreaticoduodenectomy

19. Management
• Post-operatively
 octreotide
• systemic chemotherapy
Outcomes
 Normal life expectancy for benign insulinoma
 Median period of survival is 5 years for malignant insulinomas

20. Gastrinoma
• Second most frequent
• 1-2 / million
• 60% malignant
• 75 % sporadic
• M>F
• Average age -50 years,5 to 10 years earlier in
MEN-1
• 25 % MEN-1
PASSARO TRIANGLE
70-90% found in this triangle

21. Gastrinoma
• Zollinger Ellison syndrome
• Acid Hypersecretion
• Peptic ulceration
• Multiple ulcers in atypical positions that fail to respond to angtacids
• C/F: Upper abdominal Pain
GI bleed
Severe esophagitis
Diarrhoea relieved by NG suction

22. Gastrinoma
• Investigations:
Sr Gastrin level >1000pg/ml
EUS If size < 1 cm
A combition of octreotide scan with EUS detects >90% gastrinomas
¼ th gastrinoma associated with MEN1 synd. Sr Ca++ to ruleout MEN1
syndrome

23. Gastrinoma
Treatment:
If Operable , Exploration for possible removal of tumor
Enucleation: Small lesion
Duodenum: Full thickness excision of duodenum
Pancreatic resection: Solitary gastrinoma with no mets
Hepatic Mets: Resection of mets if primary controlled
Radiofrequency ablation
Highly selective vagotomy if unresectable

24. Gastrinoma
• Long term survival is good even with mets
• 15yr survival is 80%
• Liver mets decrease survival but LN does not.

25. VIPoma (Verner-Morrison Syndrome)
• WDHA Syndrome
• Watery
• Diarrhoea(Severe interment watery diarrhoea)
• Hypokalemia
• Achlorhydria
Not revieved by NG suction
Dehydration
Weakness
K+ LOSS IN STOOLS

26. VIPoma
• 2/3rd Malignant
• Bimodal age: mostly middle age, <10 year in 10% cases
• Sr VIP level on multiple occasions (Secretion is episodic)
• EUS is most sensitive
• Management: Pre-op Aggressive hydration
Electrolyte correction
Octreotide to control diarrhoea
Simple enucleation is in adequate as it tend to be invasive
Partial pancreatic resection

27. Glucagonoma
Diabetes+ Dermatitis=
Suspicious of Glucagonoma
Necrolytic Migratory Erythema:
Bullae-> Rupture-> Bacterial and fungal
superinfection
Typically in lower abdomen ,Perineum , Perioral
and feet
Due to Severe Amino acid deficiency

28. Glucagonoma
• Glucagon is a catabolic hormone: Malnutrition
• Tumor of islet alpha cells
• More common in body and tail of pancreas
• Investigations
 Laboratory findings
 fasting glucagon level > 50 pmol/L
 Localization
 CT easily detects them
• angiography is also successful because of vascularity

29. Glucagonoma
Management
Pre-operative
 supplemental enteral nutrition
 high dose of octreotide to reverse catabolic state
• IV infusion of amino acids to reverse symptoms and improve dermatitis
 prophylaxis against thromboembolism
Operative:
 enucleation is rarely sufficient distal
pancreatectomy
• pancreaticoduodenectomy and rarely total pancreatectomy may be required

30. Somatostatinoma
• Clinical findings – unpredictable
Somatostatinoma
Biliary
Pancreatic
Insulin
Gall Stones
Steatorrhoea
Diabetes

31. Somatostatinoma
◦ Diagnosis of somatostatinomas is rarely made pre- operatively
◦ Localisation by:
◦ CT
◦ MRI
◦ Arteriography
◦ SRS

32. Non Functioning Pancreatic endocrine Tumors:
• Also called PNET(Pancreatic Neuroendocrine tumors)
• 1-2% of Pancreatic endocrine tumors and 7% of NETs.
• Symptoms similar to Pancreatic adenocarcinoma like weight loss and vague
abdominal pain
• Mostly discovered incidentally
• With advent of imaging, small PNETs(<2cm) being discovered. Some
surgeons consider observation in these cases.

33. Non Functioning Pancreatic endocrine Tumors:
• Local ablative therapies like: RFA, Cryo, and microwave coagulation
• TACE(Trans Arterial Chemo Embolisation): Palliative treatment for
Liver Mets
• Metastatic Tumor cells derive nutrition from Hepatic artery opposed to
Hepatocytes primarily from portal vein.

34. Newer Modalities:
• Peptide receptor radiotherapy
• Coupling radioactive isotopes to SSAs, which enables
selective delivery of radiotherapy to tumor cells
• PRRT(Peptide receptor radionucleide therapy) reported complete and partial
tumor response in 2% and 28% of patients respectively with median
overall survival 48 months
• PRRT is generally reserved for patients demonstrating progression of liver
metastases

35. Newer Modalities:
• SOMATOSTATIN ANALOGS
• Used since 1980’s
• Hormone blocking agents that are synthetic somatostatin derivatives (ex:
octreotide and lanreotide)
• First line for neuroendocrine gastroenteropancreatic tumors
• 2nd -3rd line for insulinomas andgastrinomas
• Side effects: development of gallstones secondary to inhibition of cholecystokinin
release, pain at site, hypo or hyperglycemia, rash, alopecia, fluid retention

36. Targeted molecular therapy:

38. Summary
• Relatively rare tumors
• The cornerstone of therapy for localized disease is surgical resection
• Most patients present with metastatic disease and will require a
multidisciplinary therapeutic approach.
• Cytoreductive surgery is generally indicated if greater than 90 percent of
the tumor burden can be removed in G1 G2 tumors
• Targeted molecular therapy - the new thing

40. Management of pNET in MEN 1
• Surgical resection of small gastrinomas and non-functional pNETs in MEN1 is
controversial.
• In favor of surgery
• Up to 33% of patients with tumors <1 cm already have metastatic disease and
that early resection is the best chance to prevent development of metastases
• The most common operation is a distal pancreatectomy with enulceation of any
tumors in the head of the pancreas

41. Management of pNET in MEN 1
• In favor of observation
• Pancreatic resection has significant morbidity and mortality.
• That given the underlying biology of the patient, resection is rarely
curative and most patients require re-operation.
• Even with metastatic disease, survival is generally excellent (roughly
50% 15-year survival rate for metastatic gastrinoma)