Pancreatic ductal adenocarcinoma
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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.
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 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
hereditary syndromes 6
There is only a weak association, if at all, with heavy alcohol consumption alone, though chronic pancreatitis is a risk factor 1.
pain (most common)
Courvoisier gallbladder: painless jaundice and enlarged gallbladder
Trousseau syndrome: migratory thrombophlebitis
new-onset diabetes mellitus
lipase hypersecretion syndrome (10-15%) 9
polyarthralgia and subcutaneous fat necrosis +/- lytic bone lesions
elevated serum lipase and eosinophilia
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.
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.
head and uncinate process: two-thirds of cases
body and tail: one-third of cases 1
Histological subtypes include:
undifferentiated carcinoma and undifferentiated with osteoclast-like giant cells 12
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
Please see pancreatic ductal adenocarcinoma staging.
Recurrence is probably better estimated by a risk score than by staging 10.
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.
Findings are non-specific and include:
double duct sign may be seen
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.
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.
General imaging differential considerations include:
the "duct penetrating sign" is an important sign to differentiate between chronic focal pancreatitis and pancreatic malignancy
other pancreatic neoplasms
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
- 1. Douglas B. Evans, Peter W.T. Pisters, James L. Abruzzese. Pancreatic Cancer. (2002) ISBN: 9780387951850 - Google Books
- 2. Frederick L. Greene, Charles M. Balch, Irvin D. Fleming et al. AJCC Cancer Staging Handbook. (2002) ISBN: 9780387952703 - Google Books
- 3. Lu D, Reber H, Krasny R, Kadell B, Sayre J. Local Staging of Pancreatic Cancer: Criteria for Unresectability of Major Vessels as Revealed by Pancreatic-Phase, Thin-Section Helical CT. AJR Am J Roentgenol. 1997;168(6):1439-43. doi:10.2214/ajr.168.6.9168704 - Pubmed
- 4. Vincent T. DeVita, Theodore S. Lawrence, Steven A. Rosenberg. DeVita, Hellman, and Rosenberg's Cancer. (2008) ISBN: 9780781772075 - Google Books
- 5. Mergo P, Helmberger T, Buetow P, Helmberger R, Ros P. Pancreatic Neoplasms: MR Imaging and Pathologic Correlation. Radiographics. 1997;17(2):281-301. doi:10.1148/radiographics.17.2.9084072 - Pubmed
- 6. Schenk M, Schwartz A, O'Neal E et al. Familial Risk of Pancreatic Cancer. J Natl Cancer Inst. 2001;93(8):640-4. doi:10.1093/jnci/93.8.640 - Pubmed
- 7. Morgan D, Waggoner C, Canon C et al. Resectability of Pancreatic Adenocarcinoma in Patients with Locally Advanced Disease Downstaged by Preoperative Therapy: A Challenge for MDCT. AJR Am J Roentgenol. 2010;194(3):615-22. doi:10.2214/AJR.08.1022 - Pubmed
- 8. Polvani S, Tarocchi M, Tempesti S, Galli A. Nuclear Receptors and Pathogenesis of Pancreatic Cancer. World J Gastroenterol. 2014;20(34):12062-81. doi:10.3748/wjg.v20.i34.12062 - Pubmed
- 9. Riediger C, Mayr M, Berger H et al. Transarterial Chemoembolization of Liver Metastases as Symptomatic Therapy of Lipase Hypersecretion Syndrome. J Clin Oncol. 2012;30(23):e209-12. doi:10.1200/JCO.2011.40.7627 - Pubmed
- 10. Kim D, Lee S, Kim S et al. Estimating Recurrence After Upfront Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma by Using Pancreatic CT: Development and Validation of a Risk Score. Radiology. 2020;296(3):541-51. doi:10.1148/radiol.2020200281 - Pubmed
- 11. Javadi S, Menias C, Korivi B et al. Pancreatic Calcifications and Calcified Pancreatic Masses: Pattern Recognition Approach on CT. AJR Am J Roentgenol. 2017;209(1):77-87. doi:10.2214/AJR.17.17862 - Pubmed
- 12. Vinay Kumar, Abul K. Abbas, Jon C. Aster. Robbins & Cotran Pathologic Basis of Disease. (2020) ISBN: 9780323531139 - Google Books