Pancreatic Cancer

Question 1

Pancreatic Cancer: The Facts

Answer 1

Question 2

Risk Factors

Answer 2

Question 3

Precursor Lesions

Answer 3

• Pancreatic Intraepithelial Neoplasia
o Premalignant lesion of the pancreatic ducts
o Stepwise progression from low grade to high grade
─ Type 1 to Type 2 to Type 3
o Associated with accumulating genetic alterations
─ KRAS, CDKN2A, P53, SMAD4

• Intraductal Papillary Mucinous Neoplasms (IPMN)
o Radiographically detectable cystic tumors
o More prevalent as you age (2% of adults, 10% age > 70) o Overall risk for pancreatic cancer ~ 25%
o High frequency of genetic mutations
─ KRAS (40-60%), GNAS (cyclic AMP amplification), RNF43 (inactivation of WNT)

Question 4

Intraductal Papillary Mucinous Neoplasms

Answer 4

Question 5

Mucinous Cystic Neoplasms (MCN)

Answer 5

• Relatively uncommon
• Most frequently occur in women (>95%)
• Always a single lesion, most commonly in the distal pancreas
• Dense ovarian like stroma surrounding mucin producing cells
• Risk of malignancy 17% if > 4 cm

Question 6

Summaries of Intraductal papillary mutinous neoplasm (IPMN) and Mucinous cystic neoplasm

Answer 6

Question 7

Pancreatic Cancer Screening

Answer 7

• Controversial
• Canto et al
  
  • Screening 225 high risk individuals (HRI) at 5 academic centers
  • CT/MRCP/EUS for each patient
  • Proven or suspected neoplasms seen in 85 HRI’s o Screening detects cysts and high-grade neoplasms (IPMN)
• Langer et al
  
  • Prospective Study
  • 76 high risk individuals with familial pancreatic cancer
  • 28 pts with abnormalities (precursor lesions to cancer, i.e. Pan-IN)
  • EUS/MRA/MRCP not justified
• Consensus guidelines (International Cancer of the Pancreas Screening)
  
  • EUS and or MRCP recommended o High volume centers

Question 8

Symptoms for Pancreatic Cancer

Answer 8

Question 9

Diagnosis

Answer 9

• Serologic Testing
• CA 19-9
• SPAN-1
  CA-50
  DUPAN-2
  Elastase-1
  Tissue polypeptide-specific antigen
• Micro-RNAs

Question 10

Diagnostic Imaging

Answer 10

• CT, MRI or MRCP
  
  • Preferred – multi-detector CT angiography
  • Allows for enhanced visualization of pancreas as well as the surrounding vasculature (vascular invasion of tumor)
• Endoscopic Retrograde Cholangio Pancreatography (ERCP)
  
  • Unable to visualize the extent of tumor
  • Tumor sampling is challenging
• Endoscopic Ultrasound (EUS)
  
  • Most sensitive for detecting small pancreatic lesions o Sampling of tumor

Question 11

Pancreas Cancer ultrasound

Answer 11

Question 12

Treatment Options – Surgery

Answer 12

Question 13

Whipple Procedure

Answer 13

• Pancreatoduodenectomy
• Standard for resectable pancreatic cancer (10% of cases)
• 5-year survival ~ 30-40%

Question 14

Non-Surgical Treatment

Answer 14

• Chemotherapy
  
  • Neoadjuvant
    
    • FOLFIRINOX, gemcitabine/abraxane
  • Adjuvant
    
    • FOLFIRINOX, chemoradiation with 5FU, gem
  • Metastatic
    
    • FOLFIRINOX, gem/abraxane, gem/erlotinib, gem/capecitabine, gem/cisplatin, gem, 5FU/liposomal irinotecan
    • Targeted therapies (eg PARP inhibitors, NTRK inhibitors)
    • Immunotherapies (MSI+ patients)
• Radiation
  
  • Concurrent RT with chemotherapy
  • SBRT
• Combination

Question 15

Prognosis

Answer 15

Best when tumor size is small and localized to the pancreas

Resection is best chance of cure

Pancreatic cancer has the lowest survival of all cancers

Question 16

Complications

Answer 16