1. Richard Zubarik, MD Professor of Medicine Director of Endoscopy
Pancreas Cancer
Richard Zubarik, MD
Professor of Medicine
Director of Endoscopy

2. Pancreas Anatomy

3. Physiology Ductal cell Islets of Langerhans
Bicarbonate, water , digestive enzyme secretion
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
Acinar cell
synthesize, store, secrete digestive enzymes
most active protein synthesizing cell in body

4. Pancreas Cancer

5. Pancreas Adenocarcinoma

6. The Numbers
4th 5%
1.4%
1 of 76
33,370

7. Pathophysiology Location: Local Invasion (most common) Distant Spread
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

8. Pathophysiology

9. Risk Factors Family History Smoking Alcohol Obesity Diabetes mellitus
Chronic pancreatitis
Familial cancer syndromes

10. Clinical Manifestations

11. 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

12. Imaging Modalities

13. Pancreas Adenocarcinoma Staging

14. Therapy-Surgery Pancreaticoduodenectomy (Whipple procedure)
Distal Pancreatectomy

15. Sener et al, J Am Coll Surg 1999;189(1):1-7.
Surgery and Survival
Sener et al, J Am Coll Surg 1999;189(1):1-7.

16. Therapy 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

17. 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
Risk of paralysis (spinal arteries)
Benefit
Duration
Narcotic use
EUS guided
78-90%
8 weeks
 Or 

18. Palliation-Biliary Obstruction

19. Palliation- 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%)

20. Pancreatic Neuroendocrine Tumors

21. 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

22. Introduction Pathophysiology Symptoms PET tumors also produce
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

23. PNET hormonal syndromes

24. MEN-1 Hyperparathyroidism 78-97% Pancreatic endocrine tumor 81-82%
Gastrinoma
54%
Insulinoma
21%
Glucagonoma 3%
VIPoma 1%
Pituitary tumors
21-65%

25. Tumor localization Goals Help localize for surgery
Detect multifocal tumors
i.e. gastrinomas
Detect metastatic disease
Avoidance of surgery

26. Tumor localization 30 35 44 31 42 70 10 27 80 54 93 81 NA Insulinoma
Other NET
Tumor detection (%)
Metastasis detection (%)
Ultrasound 30 35 44 CT 31 42 70
MRI 10 27 80
Octreoscan 54 93
EUS 81 NA
Selective venous sampling

27. Somatostatin Receptor Scan

28. Prognosis Overall Incomplete resection Liver metastasis
5- year survival
70%
43%
20%
10- year survival
50%
25%

29. 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.

32. 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

33. 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%

34. 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.

37. Data Gastrin: 470 Chromogranin A: 2480 Basal acid output 16.93
Diarrhea resolved completely with PPI

38. 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

39. Gastrinoma Symptoms: Peptic ulcer disease Diarrhea
Duodenum 75%
Uncommon sites in small bowel
Diarrhea
Volume
Duodenal pH/ malabsorption
Gastroesophageal reflux
66%

40. Gastrinoma When to think of gastrinoma:
Duodenal ulcerations in unusual places
Diarrhea in a patients with idiopathic peptic ulcer disease/GERD
Patient with idiopathic peptic ulcer disease/GERD with history of hyperparathyroidism
Prominent gastric folds on UGI or endoscopy with idiopathic peptic ulcer disease/GERD or idiopathic diarrhea

42. Gastrinoma Association 50% malignant
Sporadic (75%)
MEN-1 (25%)
50% malignant
Duodenum most common extrapancreatic site

43. Gastrinoma Fasting serum gastrin Gastric acid testing
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

44. 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.

46. Nonfunctioning Pancreatic Endocrine Tumors (PET)
Definition
PET with no clinical symptoms caused by hormone overproduction
May have elevated:
Pancreatic polypeptide
HCG
Chromogranin
Neurotensin
Usually:
Large (72%>5cm)
Malignant (64-92%)
Head

47. Nonfunctioning PET Presentation Therapy Survival Most common
Abdominal pain (36%)
Jaundice (28%)
Incidental at surgery (16%)
Therapy
Rare diagnosis established prior to surgery
Survival
44% at 5 years

48. Therapy Localized Disease Surgery
Enucleation, distal pancreatectomy, pancreaticoduodenectomy (Whipple procedure)
Tumor type influences surgery
Observation
Non-functioning tumors <2cm
Hepatic Metastasis
resection
transplantation
Hepatic artery embolization
Radiofrequency ablation/ cryoablation
Chemotherapy (rapidly growing or poorly differentiated)

49. 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