By Dr Dipesh K.K General Surgeon

1. DR. DIPESH K.K

2.  Rudolf Heidenhain discovered
neuroendocrine cells in 1870
 The first report of a PNET was done by Albert
Nicholls in 1902

3. Pancreatic endocrine tumors
(PETs) are rare neoplasms that
comprise 2% to 4% of all
clinically detected pancreatic
tumors.

4.  The origin of these tumors is not completely
understood. Based on the most recent
evidence, it has been suggested that these
tumors arise from an endocrine cell–derived
gastrointestinal epithelium.

5.  1 case per 100,000 individuals per year.
 Represent 2 – 4% of pancreatic tumors.
 Forth to sixth decade of life.
 Most pancreatic NETs are sporadic, but they can be associated with
hereditary endocrinopathies.
 MEN1. 80 – 100%
 Von Hipple Lindau (VHL). 20%
 Neurofibromatosis 1 (NF-1). 10%
 Tuberous sclerosis complex (TSC). 1%

6. Well-Differentiated Endocrine Tumor
Type 1: Benign Behavior
 Confined to the pancreas
 <2 cm in diameter
 <2 mitoses per high-powered field
 <2% Ki-67–positive cells
 No vascular or perineural invasion
Well-Differentiated Endocrine
Carcinoma
 Low-grade malignant
 Gross local invasion
 Metastases
Type 2: Uncertain Behavior
 Confined to the pancreas and one
 of the following:
 >2 cm in diameter
 >2 mitoses per high-powered field
 >2% Ki-67–positive cells
 Vascular or perineural invasion
Poorly Differentiated Carcinoma
 High-grade malignant
 >10 mitoses per high-powered field

7. T: Primary Tumor
T0: No evidence of cancer
Tis: Carcinoma in situ
T2: Tumor limited to the pancreas, size
>2 cm
T3: Tumor extends beyond the pancreas
but does not involve the celiac axis or
superior mesenteric artery
T4: Tumor involves celiac axis or
superiormesenteric artery
(unresectable primary tumor)
N: Regional Lymph Nodes
N0: No regional lymph nodes involved
N1: Regional lymph nodes involved
M: Distant Metastases
Stages
0: Tis N0 M0
IA: T1 N0 M0
IB: T2 N0 M0
IIA: T3 N0 M0
IIB: T1 N1 M0, T2 N1 M0,
T3 N1 M0
III: T4, any N, M0
IV: Any T, any N, M1

8. Based on functionality – i.e. syndrome
produced –
1.Functional
(Detected early due to
symptoms produced due to
hormone excess)
• Insulinoma
• Gastrinoma
• VIPoma
• Glucagonoma
• Somatostatinoma

9. Cell Type Hormone Produced Endocrine
Tumor/Syndrome
Alpha (A) Glucagon Glucagonoma
Beta (B) Insulin Insulinoma
Delta (D) Somatostatin Somatostatinoma
D2 VIP VIPoma
G Gastrin Gastrinoma

10.  Most common type of functioning pancreatic
endocrine tumor.
 Women (2:1)
 50 - 60 years old.
 Benign. Solitary and small.
 Can occur sporadically or in
association with the hereditary MEN-1.

11. WIPPLE TRIAD
 Whipple described a triad of signs and symptoms
associated with insulinomas
 Symptoms of hypoglycemia.
 Blood glucose < 45 mg/dL.
 Relief of symptoms with Glucose

12. SYMPTOMS OF HYPOGLYCEMIA:
 Altered mental state
 Weakness.
 Diplopia.
 Seizures.
 Coma.
 Sweating.
 Palpitations.
 Anxiety.

13.  Monitored fast for <48 hours with documented
blood glucose <50 mg/dL with hypoglycemic
symptoms
 Relief of symptoms after oral glucose load.
 Elevated insulin > 5 – 10 μU/mL.
 Increase proinsulin level > 22 pmol.
 Absence of sulfonylureas in plasma or urine.
 Elevated C peptide levels.

14.  CT has been shown to be more sensitive for detecting
small insulinomas.
 Most insulinomas are vascular and can be visualized on
arterial phase imaging.
 One series comparing the use of CT, EUS, and the two in
combination found the sensitivity of CT with EUS was
superior to either modality done separately
 MRI is considered a second-line modality in the
evaluation of insulinomas because of its greater
expense and more limited availability.

16. Fig. 1. Contrast-enhanced CT of the abdomen demonstrates
a well-circumscribed, round insulinoma (arrow) in the
body of the pancreas with homogeneous enhancement

17.  Fig:-Homogenous hypoechoic mass lesion in the head of the
pancreas adjacent to the common bile duct (CBD, above) and
portal vein (PV, below) without invasion of these structures

18.  Pathological specimen demonstrates characteristic
pale well-defined mass consistent with an

19.  The definitive treatment for patients with insulinomas is
resection of the tumor,
 Presurgical therapy to alleviate the symptoms and
neurologic affects of hypoglycemia should be instituted.
 A number of insulin antisecretagogues can be used, such as
- Diazoxide
-Verapamil
-Octreotide
-Dilantin

20.  Stabilize the glucose level with diet and/or diazoxide.
 If the tumour is exophytic or pheripheral(head,distal) by imaging
Tumour enucleation,consider laparoscopic resection
 If deeper and invasive tumour and those in proximity to MPD
Head-pancreaticoduodenectomy
Distal-distal pancreatectomy, consider laparoscopic resection
 Metastatic disease:
-If resectable then resection with octreotide and chemotherapy
-If unresectable then palliative treatment

21.  2nd most common functioning islet cell tumor of the
pancreas.
 0.5 to 3 per million population per year
 Peak age of onset is 50 years20-30% associated with
MEN1
 Zollinger Ellison syndrome – ectopic gastrin secretion
- excessive gastric acid secretion - PUD, GERD and
diarrhea.

22.  Peptic ulcer disease with
diarrhea.
 Ulcers in unusual
locations.
 Refractory to medication
ulcers.
 Young age ulcer with
complications.
 Abdominal pain.
 Chronic diarrhea.
 Heartburn.
 Nausea,Vomiting.
 Bleeding.
 Esophageal strictures.
 Pyloric or duodenal scarring.
 Prominent gastric folds

23. Differential Diagnosis of Hypergastrinemia
High Acid Output
 Zollinger-Ellison syndrome
 G-cell hyperplasia
 Retained gastric antrum
 Gastric outlet obstruction
Normal Acid Production
 Atrophic gastritis
 Proton pump inhibitors
 Postvagotomy syndrome
 Renal failure

24. Diagnostic Criteria for Gastrinoma
 Fasting gastrin level: > 100 pg/mL or >10 times
higher
than upper limit.
 Secretin stimulation test: Gastrin > 200 pg/mL.
 Calcium infusion provocative testing: Gastrin > 395
pg/dL.
 Basic acid output level > 15 mEq/L

25.  Once the biochemical diagnosis of ZES has been
established,the next step is to localize the primary
lesions and determine the presence or extent of
tumor spread by
-CT scan
-Endoscopic ultrasound.
-Somatostatin Receptor Scintigraphy.
-Intraoperative palpation and
Ultrasound.

27.  Gastrinoma Triangle: More than 80% of
gastrinomas are located within this triangle

28. The primary goal of treatment is
 To control acid production,
 Remove the primary tumor, and
 Prevent malignant progression.

29. TREATMENT
1) PPI- to control acid production
2) Surgical
 HEAD:-
 If exophytic or pheripheral tumour by imaging
Enucleation of tumour +periduodenal node dessection
 If deeper and invasive tumour and those in proximity to MPD
pancreaticoduodenectomy
 DISTAL:- Distal pancreatectomy +/- splenectomy

30.  DUODENAL TUMOUR:-
Duodenotomy and intraoperative ultrasonogram;local
resection/enucleation of tumour + periduodenal node
dissection.
 Metastatic disease:
-If resectable then resection with octreotide and
chemotherapy
-If unresectable then palliative treatment

31.  MEN-1 patients with ZES:-
 The operative role and appropriate procedure in
MEN-1 patients with ZES is controversial. (because
more than 50% of these patients are initially seen
with evidence of metastases;
 Thus MEN-1 patients are rarely cured by surgery.
 The goal of surgery in MEN-1 patients is not cure but
prevention of metastatic disease

32.  The first patient with a glucagonoma was described
in 1942 by Becker and colleagues.
 Male = Female.
 Age 50 – 60.
 Malignant 60 – 70 %
 Association with MEN-1 is rare.

33. Clinical presentation:
 Diabetes.
 Necrolytic migratory erythema.
 Deep vein thrombosis.
 Depression.
 Weight loss.
 Stomatitis.
Fig.Necrolytic migratory erythema of
glucagonoma

34. DIAGNOSIS:
 Fasting serum glucagon > 1000 pg/dL.
 Increase glucose.
 Decrease plasma amino acids
 Normochromic normocytic anemia,

35.  CT scan is sufficient for localization and has been
reported to detect 86% of tumors.
 EUS is usually unnecessary for localization, but it can
be
useful for US-guided needle biopsy.
 SRS has been used more for long-term follow-up of
these patients and can demonstrate metastatic
disease.

38.  Correction of metabolic deficits.
 Somatostatin analogues should be considered to diminish
circulating levels of glucagon
 The majority of tumors are located in the body or tail
Distal pancreatectomy with peripancreatic lymphnode
dissection with spleenectomy
 Metastatic disease:
-If resectable then resection with octreotide and
chemotherapy
-If unresectable then palliative treatment

39.  Male > Female.
 Mean age 48.
 Benign 50%
 Rare with incidence- 1 per 10 million
 Over 70% patients have metastatic disease at the time of
presentation
 Solitary, large and are usually diagnosed at >3 cm in size

 10% associated with MEN1

41.  Diagnosis
 Fasting serum VIP level should be greater than
200pg/mL; average levels are close to 1000 pg/mL in
patients with VIP tumors.
 Location: The majority of pancreatic VIP tumors are
located within the tail of the pancreas (72%)
 CT scan of theabdomen and pelvis.
for localizing these lesions approaches 100%.(Because of
their relatively large size)

42. Treatment:
 Correction of electrolyte imbalance.
 Somatostatin
 Stabilize glucose level
 The majority of tumors are located in tail
Distal pancreatectomy with peripancreatic
lymphnode
dissection with spleenectomy

43.  If tumor located in head:-
pancreatoduodenectomy with peripancreatic
lymphnode dissection
 Metastatic disease:
-If resectable then resection with octreotide
and chemotherapy
-If unresectable then palliative treatment

44.  Rare, only 1% of the Neuroendocrine tumors.
 Mean age: 50 years.
 Men = Women.
 lesions are solitary and generally average between 5
and 6 cm.
 Malignant: 60 – 70 %

45.  Clinical presentation:
Hyperglycemia.
Cholelitiasis.
Steatorrhea.
Diarrhea.
Gastric hypochloridia.
Jaundice.
 Diagnosis:
Fasting somatostatin > 30 pg/mL

46.  Most tumors located in the head of the
pancreas are large.
 Localization of pancreatic somatostatinomas
often can be accomplished by CT or US,
whereas EUS, MRI, and SRS play a role in
localization of smaller or metastatic tumors.

48.  Surgical resection is the curative treatment,
 Debulking can provide symptomatic relief
 cholecystectomy should be performed at the
time of operation because of the high incidence
of cholelithiasis.
 In unresectable disease, octreotide and
interferon-alfa may improve symptoms

49.  In patients without metastatic disease, the
mean 5-year survival is 100%.
 Those patients with metastatic disease who
undergo radical resection or debulking
procedures have a mean 5-year survival of
60%

50. NON FUNCTIONAL NEUROENDOCRINE TUMOR
- They do not present clinically with a hormonal
syndrome as compared with their functional
counterparts
- They often present later in the course of the disease
with symptoms of local compression or metastatic
disease

51.  They represent more than 75% of all
pancreatic endocrine tumors.
 lack a clinical syndrome of hormone
overproduction
 Women (2:1) , Mean age: 45yr
 60 – 80% are metastatic at diagnosis.
 60% are malignant

52.  These lesions are typically discovered on routine
radiographic imaging done for nonspecific
abdominal
complaints.
 As these tumors grow larger and begin to compress
surrounding structures, patients may develop
symptoms
of pain or obstruction.

53. Blood testing for tumor markers include
 pancreatic polypeptide,
 neurotensin,
 protein S,
 neuron-specific enolase,and
 chromogranin A.
Measurement of these levels prior to resection
may help
establish a baseline for tumor burden and
provide a
possible marker for follow-up for tumor

54.  Localization of the primary tumor and
establishment of the extent of metastatic
disease is best achieved with a triplephase—
arterial, portal, and venous phase—CT scan.
 Because these tumors are typically large,
EUS is only necessary for biopsy or to identify
subcentimeter disease.

60.  Tricia A, Moo-Young and Richard A. Endocrine tumors of the pancreas:
clinical picture, diagnosis,
 and therapy. In: Blumgart's Surgery of the Liver, Biliary Tract, and
Pancreas. 5th edition. Chapter61. Pp 934 – 944.
 Ladner D and Norton J. Neuroendocrine Tumors of the Pancreas. In:
Shackelford’s Surgery of the Alimentary Tract. 7th edition. Pp 1206 –
1216.
 http://www.uptodate.com/contents/classification-epidemiology-clinical-
presentationlocalization-and-staging-of-pancreatic-neuroendocrine-
tumors-islet-cell-tumors
 http://www.uptodate.com/contents/insulinoma?source=see_link
 http://www.uptodate.com/contents/zollinger-ellison-syndrome-
gastrinoma-clinicalmanifestations-and-diagnosis?source=see_link