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.
On imaging, it usually presents as a hypodense mass on CT that is poorly marginated, which may encase vessels and the common bile duct.
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
- chronic pancreatitis 12
- a diet rich in animal fats and protein
- diabetes mellitus
- family history: three or more first-order relatives with pancreatic cancer results in ~20x risk 8
- hereditary syndromes 6
Perhaps surprisingly there is only a weak association, if at all, with heavy alcohol consumption 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
- intraductal papillary mucinous neoplasm (IPMN)
- mucinous cystic neoplasm
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 SMA and celiac axis, which if involved exclude the patient from any attempted resection 1,2.
- adenocarcinoma: majority
- acinar cell carcinoma of the pancreas
- adenosquamous carcinoma of the pancreas
- colloid carcinoma of the pancreas
- hepatoid carcinoma of the pancreas
- medullary carcinoma of the pancreas
- signet-ring cell carcinoma of the pancreas
- 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, in more than 90%
- TP53: alterations in 70- 75%
- SMAD4: inactivated in 55%
- CKN2A: altered in 30% 12
Location and classification
- head and uncinate process: two-thirds of cases
- body and tail: one-third of cases 1
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:
- hypoechoic mass
- 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 hypodense on arterial phase scans in 75-90% of cases, but may become isodense 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 (SMA 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.
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:
- acute pancreatitis
- 'duct penetrating sign' is an important sign to differentiate between chronic focal pancreatitis and pancreatic malignancy.
- other pancreatic neoplasms
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
- periampullary tumors
- pancreatic metastases
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- 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 citation
- 10. Dong Wook Kim, Seung Soo Lee, Seon-Ok Kim, Jin Hee Kim, Hyoung Jung Kim, Jae Ho Byun, Changhoon Yoo, Kyu-pyo Kim, Ki-Byung Song, Song Cheol Kim. Estimating Recurrence after Upfront Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma by Using Pancreatic CT: Development and Validation of a Risk Score. (2020) Radiology. doi:10.1148/radiol.2020200281 - Pubmed
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