Pancreatic ductal adenocarcinoma (PDAC) makes up the vast majority (~90%) of all pancreatic neoplasms and remains a disease with a very poor prognosis and high morbidity.
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Epidemiology
Pancreatic cancer accounts for 22% of all deaths due to gastrointestinal malignancy, and 5% of all cancer deaths 1. In general, it is a malignancy of the elderly with over 80% of cases occurring after the age of 60 1.
Risk factors
Risk factors include:
cigarette smoking: the strongest environmental risk factor
a diet rich in animal fats and protein
family history: three or more first-order relatives with pancreatic cancer results in ~20x increase in risk 8
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hereditary syndromes 6
BRCA2 mutations are the most frequent cause of familial pancreatic cancer 12
familial breast cancer
There is only a weak association, if at all, with heavy alcohol consumption alone, though chronic pancreatitis is a risk factor 1.
Clinical presentation
pain (most common)
Courvoisier gallbladder: painless jaundice and enlarged gallbladder
Trousseau syndrome: migratory thrombophlebitis
new-onset diabetes mellitus
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lipase hypersecretion syndrome (10-15%) 9
polyarthralgia and subcutaneous fat necrosis +/- lytic bone lesions
elevated serum lipase and eosinophilia
Serum markers
The serum levels of these antigens are frequently raised in people with pancreatic cancer and can be used to track a patient's response to treatment. However, these markers cannot be used for population screening due to a lack of sensitivity and specificity 12.
Pathology
Three precursor lesions for pancreatic adenocarcinoma have been identified 8:
pancreatic intraepithelial neoplasia (PanIN): responsible for more than 90% of pancreatic cancers 12
Cancerous cells arise from the pancreatic ductal epithelium. As the majority of tumors (90%) 1 are not resectable, diagnosis is usually achieved with imaging (typically CT scan) although laparoscopy is often required to confirm resectability 1,2. The key to accurate staging is the assessment of the superior mesenteric artery and celiac axis, which if involved exclude the patient from any attempted resection 1,2.
Location
head and uncinate process: two-thirds of cases
body and tail: one-third of cases 1
Subtypes
Histological subtypes include:
adenocarcinoma: majority
undifferentiated carcinoma and undifferentiated with osteoclast-like giant cells 12
Genetics
The most prevalent molecular changes responsible for pancreatic carcinoma are:
KRAS: the most commonly mutated oncogene (>90%)
TP53: alterations in 70-75%
SMAD4: inactivated in 55%
CKN2A: altered in 30% 12
Staging
Please see pancreatic ductal adenocarcinoma staging.
Recurrence is probably better estimated by a risk score than by staging 10.
Radiographic features
Fluoroscopy
Barium meal / small bowel follow-through
If large enough, may demonstrate a reverse impression on the duodenum: Frostburg inverted 3 sign or a wide duodenal sweep.
Ultrasound
Findings are non-specific and include:
hypoechoic mass
double duct sign may be seen
CT
CT is the workhorse of pancreatic imaging. Typically ductal adenocarcinomas appear as poorly defined masses with extensive surrounding desmoplastic reaction. They enhance poorly compared to adjacent normal pancreatic tissue and thus appear hypoattenuating on arterial phase scans in 75-90% of cases, but may become isoattenuating on delayed scans 1 (thus the need for multiple phase scanning when pancreatic cancer is the clinical question). The double duct sign may be seen. Calcifications are very rare in adenocarcinoma and when present are more likely due to a pre-existing condition such as chronic pancreatitis 11.
CT correlates well with surgical findings in predicting unresectability (positive predictive value of 89-100% 3). The most important feature to assess locally is the relationship of the tumor to surrounding vessels (superior mesenteric artery and celiac axis). If the tumor surrounds a vessel by more than 180 degrees, then it is deemed T4 disease and is unresectable 3.
MRI
Signal characteristics include:
T1: hypointense cf. normal pancreas 5
T1 FS: hypointense cf. normal pancreas 5
T1 C+ (Gd): slower enhancement than the normal pancreas, therefore dynamic injection with fat saturation with arterial phase imaging is ideal
T2/FLAIR: variable (therefore not very useful), depending on the amount of reactive desmoplastic reaction 1,5
MRCP: double duct sign may be seen
Treatment and prognosis
Most tumors are not resectable at diagnosis.
Surgery for stage I and II (see staging of pancreatic cancer) does offer the chance of cure, though with high morbidity (20-30%) and mortality (5%) 3. Resection of pancreatic head tumors is performed with a Whipple operation.
Even when resection is possible, the majority of patients succumb to recurrence, with only a doubling of survival in operated patients 1, from 5% to 10% at 5 years 4. At 12 months following the diagnosis, almost a quarter of the patients will have died 4.
Differential diagnosis
General imaging differential considerations include:
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the "duct penetrating sign" is an important sign to differentiate between chronic focal pancreatitis and pancreatic malignancy
other pancreatic neoplasms
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fatty infiltration of the pancreatic head
usually involving the anterior portion
no secondary signs (e.g. pancreatic duct or common bile duct dilatation)
high signal on T1 and signal drop on chemical shift sequences
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