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
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.
15.
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
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.
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.
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.
36.
37.
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
40.
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 %
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.
47.
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.
55.
56.
57.
58.
59.
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.
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