Neuroendocrine tumors of Pancreas

Dr. Amit Goswami

Incidence : 1-10/million Age : 30-60years Origin:

-Immature pancreatic stem cell

-APUDomas Functional /non functional Insulinoma and gatrinoma 70%-90% Hereditary syndromes

Classification

Insulinoma

Insulinoma

Most common 60%

Origin- β cells

F>M

90% benign, 10% malignant

Most solitary, 10% multiple

21% MEN 1 – insulinomas

The median age at diagnosis- 47yrs

Whipple’s triad

Worse in morning

Weight gain

Diagnosis:

-72hrs fasting test Neuroglycopenic symptoms Serum glucose<45mg/dl Serum level of insulin >5μU/L Serum C-peptide(>0.7ng.ml),Proinsulin

7

Clinical Presentation

Non invasive

Helical / multi slice CT scan - 82-94% sensitivity.

MRI with gadolinium - 85%

DOTATOC scan

SRS -46%

Pre-op Localization

Selective angiography EUS – 77%, EUS guided FNA Portal Venous sampling-80% Calcium angiogram-90% IOUS-90%

Invasive

Management

Surgical treatment◦Therapy of choice◦Localisation+Removal with minimal morbidity◦Preoperative management

Optimization of hypoglycemia

Diazoxide

Enucleation- • <2cm any part of pancreas, not intimately associated

with the main pancreatic duct • 2-5 cm if located in the pancreatic head

Spleen-preserving distal pancreatectomy - tail of the pancreas

Whipple procedure- malignant tumours in the head

Gastrinoma

Gastrinoma /Zollinger-Ellison Syndrome

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-1Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol

2005;19:753–81.

ZES contd.

ZES contd.

Clinical Features

–Abdominal Pain 70%

–Diarrhea 70%

–Heartburn 50%

–Nausea 25%

–Vomiting 20%

–Weight Loss 15%

Diagnosis

Fasting Serum Gastrin (Cessation of PPI) Basic acid output Provocative test(Secretin stimulation test) -Rise by 200 pg/mL or more

◦ SRS: Imaging modality of choice◦ 67Ga-DOTATOC◦ MRI◦ CT scan◦ US◦ Endoscopic US with FNA◦ Angiography◦ IOUS

Localization

Medical management Surgical management

Localization and removal Whipple’sDistal pancreatectomyLymphadenectomy

Bartsch et al., 2005

10-year survival rate Sporadic ZES 95% ZES/MEN 1 86%.

Management

Cytoreductive surgery/Radiofrequency ablation

Hepatic artery embolization/Chemoembolizaion

Chemotherapy(Streptozotocin and doxorubicin +/-

5-fluorouracil): Rapidly growing tumors

Somatostatin analogue/Interferon: Slow growing

Management in advanced disease

VIPOMA(Verner-Morrison Syndrome )

0.05-0.2 new cases per million adults

Third most common neuroendocrine tumor of the

pancreas

Solitary, found in body or tail.

2/3 malignant

Male-to-female ratio in children - 1:1,

in adults. - 1:3

Constant features ◦ Watery Diarrhea ◦ Hypovolemia ◦ Hypokalemia◦ Acidosis

Variable features◦ Achlorhydria or hypochlorhydria◦ Hypercalcemia◦ Hyperglycemia◦ Flushing with rash.

VIPoma contd. Diagnostic triad

◦ Secretory diarrhea◦ High levels of circulating VIP > 150pg/ml◦ A pancreatic tumor

Localization◦ SRS - 91% of primary tumors and 75% of metastases.

Nikou GC, et al. Hepatogastroenterology  2005

◦ Endoscopic ultrasound.◦ CT ◦ MRI ◦ Arteriography◦ IOUS

Management Correction of metabolic abnormalityOctreotideDistal pancreatectomy/Debulking

VIPoma contd.

Glucagonoma

Tumor of islet alpha cells

Mainly body and tail

1% of all neuroendocrine tumors

Mean age of 55 years (19-84 years).

M:F - 1:3

Nearly all are malignant

Glucagonoma contd.

Plasma glucagon >1000pg/ml: Diagnostic

Enhanced CT scan

MRI

SRS

70%- Metastasis at presentation

Diagnosis

Pre-op preparation

Distal pancreatectomy

HACE

Chemotherapy

Management

somatostatinoma

Rare 70% to 90% of tumors – malignant Location – usually head Clinical findings – unpredictable

◦ Diarrhea ◦ Gallstones◦ Steatorrhea◦ Mild diabetes

Localization◦ CT◦ MRI◦ Arteriography◦ SRS

Somatostatinoma

Management -Whipple’s

-Debulking -Cholecystectomy

Somatostatinoma

Nonfunctioning Endocrine Tumors

Incidence :15%-50% Malignant ,Metastasis-60% Complaints

◦ Abdominal pain ◦ Jaundice

Surgical resection Prognosis - poor Resistant to chemotherapy Hepatic embolisation.

Management of Pancreatic Endocrine Tumors in MEN 1

Pancreatic endocrine tumors -80% MEN 1 Patients with MEN 1 -decreased life expectancy Nonfunctioning pancreatic endocrine tumors –most

common 80-100% of cases Gastrinomas -most common functional tumor

- 60% of MEN 1

PET & MEN 1

Surgical Treatment Options◦ Role of surgery in MEN 1 : controversial◦ Surgery may be indicated in patients with no distant

metastases

The goals of surgical therapy

◦ Controlling the symptoms of hormone excess◦ Safely resecting the maximal amount of tumor mass

possible◦ Preserving the maximal amount of pancreatic parenchyma

possible

What’s new?!

Activation of mTOR and VEGF pathways

Everolimus+/-Octreotide:Moderately effective(PhaseI/

II trial)

Role of Sumitinib(Phase III trial)

Combination of TACE and resection more effacicous

than each procedure alone

ASCO Gastro-intestinal cancer sympossium,2010

Just a Sunrise!

Journey Continues……..

THANK YOU