Pancreas Cancer
Richard Zubarik, MD
Professor of Medicine
Director of Endoscopy
Pancreas Anatomy
Physiology
Ductal cell
Bicarbonate, water , digestive enzyme
secretion
Acinar cell
synthesize, store, secrete digestive enzymes
most active protein synthesizing cell in body
Islets of Langerhans
Hormones secreted directly into blood flow
Alpha cell-glucagon
Beta cell- insulin and amylin
Delta cells- somatostatin
gamma cells- pancreatic polypeptide
Epsion cells- ghrelin
Pancreas Cancer
Pancreas Adenocarcinoma
The Numbers
4th
5%
1.4%
1 of 76
33,370
Pathophysiology
• Location:
– 80% head
– 70% biliary obstruction
• Local Invasion (most common)
– Stomach, Duodenum, Colon, Portal or Superior
Mesenteric Veins, Superior Mesenteric Artery
• Distant Spread
– Liver, Peritoneum, Lung
• Desmoplastic lesions
Pathophysiology
Risk Factors
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Family History
Smoking
Alcohol
Obesity
Diabetes mellitus
Chronic pancreatitis
Familial cancer syndromes
Clinical Manifestations
Serum CA 19-9
• Monosialoganglioside/glycolipid
• Advantages:
– Accessible
– Relatively sensitive/ specific for pancreatic cancer
• Levels correlate with:
– tumor size
– stage
• Present uses:
– Prognosis
– Monitor disease progression
Imaging Modalities
Pancreas Adenocarcinoma
Staging
Therapy-Surgery
Pancreaticoduodenectomy
(Whipple procedure)
Distal
Pancreatectomy
Surgery and Survival
Sener et al, J Am Coll Surg 1999;189(1):1-7.
Therapy
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General Principles
– MDC
Management of resectable disease
– Surgery
– Neoadjuvant
• Controversial, may downstage disease
– Adjuvant
• Chemotherapy beneficial
• Radiotherapy is controversial
Management of Locally advanced disease
– Chemoradiotherapy downstages 30% to resectable
Management of metastatic disease
– Gemcitabine –based combination treatments
Palliation-Pain
• Celiac plexus neurolysis:
– Anterior transgastric approach
• CT or fluroscopy- percutaneous
– Traverse bowel, further for needle to traverse, not real-time
• EUS- through stomach
– Stomach adjacent to celiac trunk, real-time
– Posterior approach
EUS
guided
Benefit
Duration
Narcotic
use
78-90%
8 weeks
 Or 
• CT or fluroscopy- percutaneous
– Risk of paralysis (spinal arteries)
Palliation-Biliary Obstruction
Palliation- Gastric Outlet Obstruction
• Gastric Outlet Obstruction
– Improved dietary performance (86%)
– Comparison with surgery (2 studies)
• Shorter time to oral intake
• Shorter hospital stay
• Complication rates
– Endoscopic (0%)
– Open (37.5%)
– Laparoscopic (42.9%)
Pancreatic Neuroendocrine
Tumors
Introduction
• Incidence 4/ 1 million population
• Classification A (PNET)
– Functional- clinical syndrome caused by hormone
release
– Non-functional
• Classification B (NET)
– Well-differentiated endocrine tumor
• Benign behavior
• Uncertain behavior
– Poorly-differentiated endocrine tumor
– Mixed exocrine-endocrine tumors
Introduction
• Pathophysiology
– Symptoms
• inappropriate biologically active peptide release
• Tumor mass effect
– PET tumors also produce
• Chromogranins (chromogranin A)
• Alpha or Beta subunit of HCG
– Peptides often released even in “non-functional”
tumors that do not cause a clinical syndrome
– Often multiple hormones released, but multiple tumor
syndromes not common
– Symptoms from hormones predate tumor symptoms
PNET hormonal syndromes
MEN-1
Hyperparathyroidism
78-97%
Pancreatic endocrine tumor
81-82%
Pituitary tumors
Gastrinoma
54%
Insulinoma
21%
Glucagonoma
3%
VIPoma
1%
21-65%
Tumor localization
• Goals
– Help localize for surgery
– Detect multifocal tumors
• i.e. gastrinomas
– Detect metastatic disease
• Avoidance of surgery
Tumor localization
Insulinoma
Other NET
Other NET
Tumor detection
(%)
Tumor detection
(%)
Metastasis
detection (%)
Ultrasound
30
35
44
CT
31
42
70
MRI
10
27
80
Octreoscan
54
70
93
EUS
81
70
NA
Selective venous
sampling
54
70
93
Somatostatin Receptor Scan
Prognosis
Overall
Incomplete Liver
resection
metastasis
5- year
survival
70%
43%
10- year
survival
50%
25%
20%
Case 1
• 44 YO white male weighing 325 pounds
who became agitated, confused after
awakening. He had accompanying
palpitations, headache and sweating. He
had elevated insulin and proinsulin levels
while fasting and a fasting glucose <35.
Computed tomography and Octreoscan
were negative.
Insulinoma
• Whipples triad (not specific)
– Hypoglycemic symptoms
– Blood sugar <50
– Symptom relief with glucose ingestion
• Symptoms (fasting, exercise, missed meal)
– Neurologic neuroglycopenia
• Headache, confusion, lightheadedness, visual disturbance,
irrational behavior, drowsiness, coma
– Catecholemine release
• Palpitations, tremor, sweating, irritability
Insulinoma
• Characteristics
– Most confined to pancreas
– Solitary
• Equal distribution in pancreas
• Usually not malignant (10%)
• Diagnosis
– 72 hour fasting glucose and insulin test
• Surgical cure rate 70-95%
Patient 2
• 41 YO male presented to clinic for a
second opinion with watery bowel
movements 5 times per day. He had mild
diffuse abdominal discomfort, and had lost
20 pounds over the last year. He saw
another gastroenterologist for this problem
3 years prior who did stool samples and a
colonoscopy that was normal. He also had
seen a naturopath.
Data
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Gastrin: 470
Chromogranin A: 2480
Basal acid output 16.93
Diarrhea resolved completely with PPI
Gastrinoma
• Zollinger Ellison Syndrome- gastric acid
hypersecretion due to release of gastrin
from and endocrine neoplasm
• Gastrin (gastric antrum):
– Primary stimulant of post-prandial acid
secretion
– Trophic effect on gastric tissue (parietal cells)
– Adult pancreas does not secrete gastrin
Gastrinoma
• Symptoms:
– Peptic ulcer disease
• Duodenum 75%
• Uncommon sites in small bowel
– Diarrhea
• Volume
• Duodenal pH/ malabsorption
– Gastroesophageal reflux
• 66%
Gastrinoma
•
When to think of gastrinoma:
1. Duodenal ulcerations in unusual places
2. Diarrhea in a patients with idiopathic peptic
ulcer disease/GERD
3. Patient with idiopathic peptic ulcer
disease/GERD with history of
hyperparathyroidism
4. Prominent gastric folds on UGI or
endoscopy with idiopathic peptic ulcer
disease/GERD or idiopathic diarrhea
Gastrinoma
• Association
– Sporadic (75%)
– MEN-1 (25%)
• 50% malignant
• Duodenum most common extrapancreatic
site
Gastrinoma
• Fasting serum gastrin
– 98% have elevated levels
– 60% of ZES patients have mild to moderate elevation
– Common differential: atrophic gastritis, PPI intake
(look at gastric folds)
• Gastric acid testing
– Gastric pH <2
– BAO >10 meq/hour (94% of ZES patients)
• Secretin injection test
– Sensitivity 87-93%; specificity > 90%
– Secretin promotes gastrin release in ZES
– 2 μg/KG prompts rise >200 pg/ml
Patient 3
• SB is a 32 Y.O. female with abdominal
distention and pain. She had an UGI that
was mildly irregular at the duodenal
sweep. CT showed a small hypervascular
lesion in the neck of the pancreas c/w a
NET. ACTH,calcitonin,gastrin,
somatostatin,insulin and glucagon levels
were normal. Calcium and CBC normal.
Pancreatic polypeptide was 353 (normal
<249). An EUS was performed.
Nonfunctioning Pancreatic
Endocrine Tumors (PET)
• Definition
– PET with no clinical symptoms caused by hormone
overproduction
• May have elevated:
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–
–
–
Pancreatic polypeptide
HCG
Chromogranin
Neurotensin
• Usually:
– Large (72%>5cm)
– Malignant (64-92%)
– Head
Nonfunctioning PET
• Presentation
– Most common
• Abdominal pain (36%)
• Jaundice (28%)
• Incidental at surgery (16%)
• Therapy
– Rare diagnosis established prior to surgery
• Survival
– 44% at 5 years
Therapy
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•
Localized Disease
– Surgery
• Enucleation, distal pancreatectomy, pancreaticoduodenectomy
(Whipple procedure)
• Tumor type influences surgery
– Observation
• Non-functioning tumors <2cm
Hepatic Metastasis
– Surgery
• resection
• transplantation
– Hepatic artery embolization
– Radiofrequency ablation/ cryoablation
– Chemotherapy (rapidly growing or poorly differentiated)
Summary
• Pancreatic cancer can be exocrine or endocrine in
nature.
• Pancreatic adenocarcinoma (exocrine) is most common.
• The 5-year survival for pancreatic adenocarcinoma (5%)
is much worse than for PNET’s.
• Pancreatic neuroendocrine tumors (endocrine) can
cause symptoms from secreted biologically active
peptides or from tumor effect
• Surgery is the only curative therapy for pancreatic
cancer, but may not be needed in small non-functional
pancreatic neuroendocrine tumors