Neuroendocrine Tumors of the
Pancreas
JOSHUA M.V. MAMMEN MD PHD FACS
Overview of Talk
 Non-functional Pancreatic Endocrine Tumors
 Functional Pancreatic Endocrine Tumors
Nonfunctional Pancreatic
endocrine tumors
Background
 58-85% of PET’s are non-functional
 Most common location is the pancreatic head
 Due to lack of symptoms, tend to present with a large
size
 Median survival: 3.2 years (7.1 years if potentially
resectable)
 Presentation:




Abdominal pain
Weight loss
Obstructive jaudice
Bowel obstruction
Diagnosis
 Usually diagnosed by CT
scan or MRI
 Endoscopic ultrasound is
more sensitive for smaller
lesions
 Octreotide imaging may
help find additional lesions
 75% are secreting
hormones in an occult
fashion (chromogranin A,
pancreatic polypeptitide)
Treatment
 Only potentially curative strategy is surgical




resection with regional lymphadenectomy
Imaging studies should be performed to assess for
resectability
Incomplete resection or debulking is not
recommended
Consider chemo or radio or bland embolization of
hepatic metastases in setting of unresectable disease
May consider observation for low grade/slow
growing disease
Treatment
 Systemic treatment
 Streptozocin based chemotherapy (up to 39% response in
combination)

Octreotide
Functional Pancreatic
Endocrine Tumors
Insulinoma
 First described in 1935 by Whipple and Frantz
 Most common functional PNET
 Triad of symptoms (Whipple’s triad):
 Hypoglcemic symptoms when fasting
 Blood glucose level of less than 50
 Symptom relief with glucose
Insulnoma
 10% Malignant
 10% Multiple
 10% associated with MEN1
Insulinoma: Diagnosis
 72 hour monitored fast
 Draw plasma glucose, C-peptide, proinsulin, and insulin every
6 hours
 Continue test until plasma glucose is less than 45 and patient
has symptoms
 Criteria for diagnosis:
 Insulin concentration greater than 6 uU/mL
 Insulin to glucose ratio greater than 0.3
 C-peptide level greater than 0.2 nmol/L
 Proinsulin level greater than 5pmol/L
 Lack of plasma sulfonylurea
Insulinoma: Diagnosis
 Exogenous insulin
 Low C-peptide levels
 Low proinsulin levels
 Oral hypoglycemic agents
 Elevated C-peptide levels
 Elevated proinsulin levels
 Plasma sulfonylurea
Insulinoma: Treatment
 Surgical resection is the main treatment
 Prior to surgery, control glucose with small meals
and diazoxide
 Use intraoperative ultrasound to identify additional
lesions at the time of surgery
 Does not require anatomic resection, merely
enucleation
 If there is evidence of malignancy, should attempt
formal resection (median disease free survival is 5
years)
Gastrinoma
 First described by Zollinger and Ellison in 1955
 Secretes gastrin that leads to hyperchlorhydria and
parietal cell hyperplasia
 Triad
 Atypical peptide ulcerations
 Gastric hypersecretion with hyperacidity
 Noninsulin producing islet tumor of the pancreas
Gastrinoma
 Sporadic gastrinomas (75%) usually present at 45
years old
 Majority (60%-90%) are malignant
 Location

63% are in the pancreatic head
 Presentation
 Abdominal pain (75%-100%
 Diarrhea (35%-73%)
 Heartburn (44%-64%)
 Duodenal and Prepyloric ulcers (71%-91%)
Gastrinoma: Diagnosis
 Carefully should withdraw PPI use
 Fasting gastrin level of greater than 1000 pg/mL and
pH less than 2.5
 Diagnosis requires:


Basal acid output greater than 15 mEq/hour
Positive secretin stimulation test
Adminster 2 units/kg intravenous secretin after overnight fast
 Draw gastrin levels prior to secretin and at 0, 2, 5, 10, and 20
minutes
 Positive is increase in serum gastrin over 200 pg/mL

Gastrinoma: Diagnosis
 CT and MRI can localize larger lesions
 Endoscopic ultrasound for smaller lesions
 Octreotide Imaging
 Selective angiography and selective arterial secretin
injection
Diagnosis: Treatment
 Initial treatment is PPI or H2 blocker
 Perform enuclation or resection with associated
lymph nodes if can be identified
 If cannot identify preoperatively, surgical
exploration with intraoperative ultrasound
 Isolated liver metastases should be resected
Vasoactive Intestinal Polypeptidoma
 Tumors secrete vasoactive intestinal polypeptide
(also known as Vener-Morrison syndrome or watery
diarrhea hypokalemia-achlorhydria syndromeWDHA)
 Presentation:
 Large volume secretary diarrhea
 Electrolyte imbalances (hypocholorhydria)
 Flushing
Vasoactive Intestinal Polypeptidoma
 60-80% are malignant at presentation
 5- year survival is 69%
 80% are isolated to the pancreas
 Diagnosis:
 Fasting plasma vasoactive intestinal polypeptide levels greater
than 500 pg/mL
 High volume diarrhea
 Imaging studies
Vasoactive Intestinal Polypeptidoma
 Treatment is surgical resection with
lymphadenectomy
 Need to hydrate and correct electrolytes prior to
surgery
 Streptozocin based chemotherapy if unresectable
Glucagonoma
 Arise pancreatic alpha
cells
 Cause increased
glucagon secretion with
glucose intolerance,
weight loss,
neuropsychiatric
disturbances, venous
thrombosis, and
necrolytic migratory
erythema
Glucagonoma
 Diagnosis
 Inappropriately elevated fasting glucagon grweater than 500
pg/mL
 Biopsy of necrolytic migratory erythema
 Imaging to identify location
Somatostatinoma
 Arise from delta cells of the pancreas
 Majority are sporadic (90%)
 Most likely to be located in the pancreas
 Presentation:
 Diabetes mellitus
 Cholelithiasis
 Steatorrhea
 Weight loss
 Anemia
 Diarrhea
Somatostatinoma
 Somatostatin level greater than 100 pg/mL
 Localize with imaging
 Typically present late
 Treatment is surgical resection with
lymphadenectomy
 Tumor debulking for palliation
 Always perform cholecystectomy due to cholestasis
Summary
 Generally, treatment is surgical resection for
sporadic cases
 Functional tumors have specific tests that help in
diagnosis