II. Epidemiology
- Third leading cause of cancer deaths in United States
-
Incidence: 2% of new cancers in United States
- New cases: 56,770 cases in 2019 (US)
- Mortality: 45,750 deaths in 2019 (US)
- Age
- Typically over age 50 years old
III. Risk Factors
- Mild Risk Factors (<5 fold increased risk)
- Alcohol use >4 drinks/day
- Obesity with Body Mass Index (BMI) >30 kg/m2
- BRCA1 gene carrier
- Polycyclic or chlorinated Hydrocarbon exposure
- Diabetes Mellitus Type II (for 5 years or more)
- Familial Adenomatous Polyposis
- Familial nonpolyposis Colorectal Cancer
- Family History: 1 first degree relative with Pancreatic Cancer
- Tobacco Abuse or exposure
- Responsible for 25-30% of Pancreatic Cancer
- Moderate Risk Factors (5-10 fold increased risk)
- BRCA2 gene carrier
- Chronic Pancreatitis
- Cystic Fibrosis
- Family History: 2 first degree relatives with Pancreatic Cancer
- Severe Risk Factors (>10 fold increased risk)
- Familial atypical multiple mole Melanoma
- Family History: 3 or more first, second or third degree relatives with Pancreatic Cancer
- Hereditary Pancreatitis
- Peutz-Jeghers Syndrome
- References
- Brand (2007) Gut 56(10): 1460-9
IV. Pathophysiology
- Adenocarcinoma of pancreatic ductal epithelium (90% of cases)
- Onset usually in head of Pancreas
V. Symptoms: General
- Common
- Unexplained Weight Loss (>5 pounds per month)
- Epigastric Abdominal Pain radiating to back
- Nonspecific associated symptoms
- Other presentations
- New onset Type II Diabetes Mellitus in a thin patient over age 50 years old
- Recurring Superficial Thrombophlebitis
VI. Symptoms: Head of Pancreas involved
- Head of Pancreas involved in two thirds of Pancreatic Cancers
- Biliary duct obstruction related symptoms
- Jaundice
- Dark Urine
- Acholic stool (Light colored stool)
VII. Signs
- Non-specific findings
- Courvoisier's Sign
- Non-tender, but distended, palpable Gall Bladder
- Associated with Jaundice
- Test Sensitivity only <56%, but Test Specificity >82%
- Other findings
- Left Supraclavicular Lymphadenopathy involving Virchow's Node
- Subcutaneous Nodules of fat or pancreatitic Panniculitis (rare)
VIII. Differential Diagnosis
- Gall Bladder Disorders (e.g. Cholecystitis, Cholelithiasis or Choledocholithiasis)
- Peptic Ulcer Disease or Gastritis
- Pancreatitis
- Abdominal Aortic Aneurysm
- Other abdominal cancer
- Liver cancer (or liver metastases)
- Lymphoma
- Stomach Cancer
- Colon Cancer
IX. Labs
-
General markers (if biliary duct obstruction)
- Alkaline Phosphatase increased
- Conjugated Serum Bilirubin increased
- Tumor Markers
X. Imaging
- Routine screening not recommended in general
- Consider endoscopic Ultrasound if Family History or other high risk factors listed above
- Initial testing
- Standard CT Abdomen
- Transabdominal Ultrasound
- Reflex to CT Abdomen if non-diagnostic
- Most accurate testing
- Triple-phase helical CT with Pancreas protocol (preferred)
- Includes imaging during arterial, late and venous phases
- Endoscopic Ultrasound
- Indicated if helical CT not diagnostic or for biposy
- Guides FNA in non-operable cancer
- Triple-phase helical CT with Pancreas protocol (preferred)
- Other testing
- MRI Abdomen with contrast (and MR cholangiopancreatography)
- Indicated if CT contrast is contraindicated or to define extrapancreatic disease
- MRI is less sensitive than CT Abdomen (with Pancreas protocol) in initial evaluation
- MRI Abdomen with contrast (and MR cholangiopancreatography)
XI. Evaluation: Suspected Pancreatic Cancer
- Metastatic cancer
- Endoscopic Ultrasound with fine needle aspirate
- No metastatic disease
- Multidisciplinary review (oncology, surgery, radiology, pathology)
- Liver Function Tests
- Chest imaging
- Consider endoscopic Ultrasound with fine needle aspirate
- Consider other imaging (e.g. MRI)
- Indicated if Pancreatic Cancer suspected but non-diagnostic triple-phase helical CT with Pancreas protocol
- Consider diagnostic staging laparoscopy
- Exclude occult peritoneal metastases
XII. Evaluation: Pancreatic Cyst evaluation
- Endoscopic Ultrasound with fine needle aspirate
- Concerning Pancreatic Cystic lesions
- Pancreatic serous cystadenoma
- Pancreatic mucinous cystic neoplasm
- Pancreatic intraductal papillary mucinous neoplasm (and other pancreatic duct dilitations)
- Pancreatic Cystic endocrine tumor
- Pancreatic ductal adenocarcinoma
XIII. Staging
- Protocol
- Based on evaluation including imaging and biopsy as described above
- Multidisciplinary Consultation
- Stages
- Localized within Pancreas, resectable (Stage 0, IA and IB)
- Classification: Tis-T2, N0, M0
- Found this early in only 8% of patients
- Five year survival: 21.5% for Stage 0 and 12% for Stage Ib
- Locally invasive, resectable (Stage IIA, IIB)
- Classification: T1-3 N0-1, M0
- Found at this stage in only 27% of patients
- Five year survival: 5-7%
- Locally advanced, NOT-resectable (Stage III)
- Classification: T4 N0-1 M0
- Five year survival: 3%
- Metastatic disease, NOT resectable (Stage IV)
- Classification: T1-4, N0-1, M1
- Found at this stage in only 53% of patients
- Five year survival: 1.9%
- Localized within Pancreas, resectable (Stage 0, IA and IB)
- Stages: Summary
- Resectable (15% five year survival)
- Accounts for 15-20% of Pancreatic Cancer cases
- Resectability is defined by degree of SMA, SMV or Portal Vein involvement
- Invasion of aorta, inferior vena cava or distant metastases excludes resection
- Body or tail Pancreatic Cancer more advanced at presentation
- Less commonly resectable at presentation than cancer involving the pancreatic head
- Locally advanced (3% five year survival)
- Metastatic (1.9% five year survival)
- Resectable (15% five year survival)
XIV. Management: General
- See Cachexia in Cancer
- See Mood Disorders in Cancer
- Treat Cancer Pain
- See Cancer Pain Management
- Celiac plexus neurolysis (via endoscopic Ultrasound)
- Alcohol injected into celiac plexus
- Significantly reduces pain
- Pancreatic Cancer specific concerns
- Malabsorption from exocrine pancreatic insufficiency
- Pancrealipase 30,000 IU
- Taken before, during and after meal
- Jaundice secondary to biliary obstruction
- Biliary decompression via surgery or endoscopy
XV. Management: Resectable Pancreatic Cancer
- Criteria for resectable cancer
- No distant metastatic cancer
- No vascular invasion
- No superior Mesenteric Artery involvement
- No aorta or inferior vena cava involvement
- No celiac involvement
- Surgery
- Performed at high volume center (>15 pancreatic resections annually)
- Cancer involving head of Pancreas: Whipple Procedure
- Classic pancreaticoduodenectomy
- Resection of pancreatic head as well as Gall Bladder, common bile duct and second part of duodenum AND
- Distal Stomach
- Pylorus-Preserving Pancreaticoduodenostomy
- Resection of pancreatic head as well as Gall Bladder, common bile duct and second part of duodenum AND
- Postpyloric duodenum
- Classic pancreaticoduodenectomy
- Cancer involing body and tail of Pancreas
- Distal pancreatectomy with or without splenectomy
- Resection is rarely possible due to delayed presentation with advanced disease
- Adjuvant Chemotherapy
- Leucovorin and fluorouracil apper to be effective
- Gemcitabine (Gemzar) also appears effective
- Radiation associated with worse prognosis
- Post-resection surveillance
- History and physical exam every 3-6 months for 2 years, then yearly
- Diagnostic options every 3-6 months
- Cancer Antigen 19-9
- Triple-Phase CT Abdomen - Pancreas protocol
- Endoscopic Ultrasound
XVI. Management: Locally advanced Pancreatic Cancer
- Combination protocol: Chemoradiotherapy
- Radiation Therapy and
- Fluorouracil or Gemcitabine
- Efficacy
- One year survival: 40% (versus 10% with no treatment)
XVII. Management: Metastatic Pancreatic Cancer - Chemotherapy and radiation options
- Precaution
- Chemotherapy and/or radiation only prolong median survival to 10.`5 months over 6.9 months
- Consider Gemcitabine
- Improves 1 year survival
- May be used in combination with fluorouracil, cisplatin and oxaliplatin
- Consider Irinotecan (Camptosar)
- Improves progression free and overall survival, but toxicity may limit tolerability
- Consider intensity-modulated Radiotherapy or stereotactic body Radiotherapy
- Localized radiation to the Pancreatic Cancer
XVIII. Management: Metastatic Pancreatic Cancer - Palliative Care
-
General measures
- Involve Hospice early
- Palliative pain management
- Depression Management
- Biliary obstruction (65-75% of patients)
- Endoscopic metal biliary stent placement
- Gastric outlet obstruction (10-25% of patients)
- Enteral stent (if Life Expectancy <3 months) or
- Gastrojejunostomy tube
- Exocrine pancreatic insufficiency
- Oral Pancreatic Enzyme Replacement
- Adjust dosing based on body weight change
- Recurrent Venous Thromboembolism Prevention
- Low Molecular Weight Heparin (instead of Warfarin)
XIX. Prevention
- Fruit and vegetables in diet
- Exercise
- NSAIDs (possible)
- Screening indications
- Moderate to high risk of Pancreatic Cancer may prompt screening with CT Abdomen or endoscopic Ultrasound
XX. Prognosis
- At diagnosis, only 15-20% of cancers are localized
- Five year survival
- Localized Pancreatic Cancer: 37.4%
- Regional Pancreatic Cancer: 12.4%
- Metastatic Pancreatic Cancer: 2.9%
- Best prognostic findings post-resection
- Negative margins
- Tumor DNA content
- Smaller pancreatic tumor size
- No Lymph Node metastases
XXI. Resources
- Pancreatic Cancer Statistics (NCI)