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Pancreatic Cancer
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Pancreatic Cancer
, Pancreatic Adenocarcinoma, Courvoisier's Sign
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
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
Pathophysiology
Adenocarcinoma of pancreatic ductal epithelium (90% of cases)
Onset usually in head of
Pancreas
Symptoms
Gene
ral
Common
Unexplained Weight Loss
(>5 pounds per month)
Epigastric Abdominal Pain
radiating to back
Nonspecific associated symptoms
Nausea
or
Vomiting
Anorexia
Early satiety
Weakness
Other presentations
New onset
Type II Diabetes Mellitus
in a thin patient over age 50 years old
Recurring
Superficial Thrombophlebitis
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)
Signs
Non-specific findings
Cachectic patient
Bruising
Jaundice
(if biliary duct obstruction)
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 Nodule
s of fat or pancreatitic
Panniculitis
(rare)
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
Labs
Gene
ral markers (if biliary duct obstruction)
Alkaline Phosphatase
increased
Conjugated
Serum Bilirubin
increased
Tumor Marker
s
CA 19-9
(use for diagnosis/prognosis, NOT screening)
bHCG (better prognostic indicator than
CA 19-9
)
CA 72-4 (better prognostic indicator than
CA 19-9
)
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
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
Evaluation
Suspected Pancreatic Cancer
Metastatic cancer
Endoscopic
Ultrasound
with fine needle aspirate
No metastatic disease
Multidisciplinary review (oncology, surgery, radiology, pathology)
Liver Function Test
s
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
Evaluation
Pancreatic Cyst
evaluation
Endoscopic
Ultrasound
with fine needle aspirate
Concerning
Pancreatic Cyst
ic lesions
Pancreatic serous cystadenoma
Pancreatic mucinous cystic neoplasm
Pancreatic intraductal papillary mucinous neoplasm (and other pancreatic duct dilitations)
Pancreatic Cyst
ic endocrine tumor
Pancreatic ductal adenocarcinoma
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%
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)
Management
Gene
ral
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
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
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
Management
Locally advanced Pancreatic Cancer
Combination protocol: Chemoradiotherapy
Radiation Therapy
and
Fluorouracil or Gemcitabine
Efficacy
One year survival: 40% (versus 10% with no treatment)
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
Management
Metastatic Pancreatic Cancer -
Palliative Care
Gene
ral 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
)
Prevention
Fruit and vegetables in diet
Exercise
NSAID
s (possible)
Screening indications
Moderate to high risk of Pancreatic Cancer may prompt screening with
CT Abdomen
or endoscopic
Ultrasound
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
Resources
Pancreatic Cancer Statistics (NCI)
https://seer.cancer.gov/statfacts/html/pancreas.html
References
(2019) Am Fam Physician 100(12): 770A-C [PubMed]
De La Cruz (2014) Am Fam Physician 89(8): 626-32 [PubMed]
Freelove (2006) Am Fam Physician 73(3):485-92 [PubMed]
Li (2004) Lancet 363:1049-57 [PubMed]
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