neuroendocrine tumors of pancreas
TRANSCRIPT
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