Pancreatic ductal adenocarcinoma

Last revised by Henry Knipe on 18 May 2024

Pancreatic ductal adenocarcinoma, frequently referred to as pancreatic cancer, 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:

There is only a weak association, if at all, with heavy alcohol consumption alone, though chronic pancreatitis is a risk factor 1.

Three precursor lesions for pancreatic adenocarcinoma have been identified 8:

Cancerous cells arise from the pancreatic ductal epithelium.

  • head and uncinate process: two-thirds of cases

  • body and tail: one-third of cases 1

Histological subtypes include:

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.

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.

As the majority of tumors (90%) 1 are not resectable, diagnosis is usually achieved with imaging (typically CT) 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.

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:

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

Most tumors are not resectable at diagnosis. The main criteria for the unresectability of pancreatic ductal adenocarcinoma are the presence of metastasis and/or vascular invasion, particularly encasement of the celiac trunk and superior mesenteric artery.

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:

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