Imaging of pancreatic cancer: An overview
Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri, USA
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Review Article
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Abstract
Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death in the United States. The median size of pancreatic
adenocarcinoma at the time of diagnosis is about 31 mm and has not changed significantly in last three decades
despite major advances in imaging technology that can help diagnose increasingly smaller tumors. This is largely because
patients are asymptomatic till late in course of pancreatic cancer or have nonspecific symptoms. Increased awareness
of pancreatic cancer amongst the clinicians and knowledge of the available imaging modalities and their optimal use in
evaluation of patients suspected to have pancreatic cancer can potentially help in diagnosing more early stage tumors.
Another major challenge in the management of patients with pancreatic cancer involves reliable determination of resectability.
Only about 10% of pancreatic adenocarcinomas are resectable at the time of diagnosis and would potentially
benefit from a R0 surgical resection. The final determination of resectability cannot be made until late during surgical
resection. Failure to identify unresectable tumor pre-operatively can result in considerable morbidity and mortality due
to an unnecessary surgery. In this review, we review the relative advantages and shortcomings of imaging modalities
available for evaluation of patients with suspected pancreatic cancer and for preoperative determination of resectability.
Key words
Pancreatic cancer; Ultrasound; Computed tomography; Magnetic resonance imaging; Endoscopic ultrasound guided
fine needle aspiration
J Gastrointest Oncol 2011; 2: 168-174. DOI: 10.3978/j.issn.2078-6891.2011.036
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Introduction
Pancreatic cancer (PaCa) is the fourth leading cause of
cancer-related death in the United States. In 2010, there
were over 43,000 estimated new cases of PaCa and over
36,000 deaths attributed to it in the United States (1). The
estimated lifetime risk of developing PaCa is about 1 in 71
(1.41%) (2). The disease is rare before age 45 but incidence
rises rapidly after that and peaks in the seventh decade of
life. The major risk factors include smoking (3), hereditary
predisposition to PaCa itself or to multiple cancers (4) and
to a lesser degree, chronic pancreatitis (5). PaCa does not exhibit early symptoms and initial symptoms are often
nonspecific. Classical presentation of PaCa (painless
jaundice) is present in only 13-18% of the patients and is
often accompanied by pruritus, acholic stools dark urine,
and weight loss (6). Abdominal pain is present in 80-85% of
patients with locally advanced or advanced disease. Acute
pancreatitis and new onset diabetes mellitus can often be
the initial presentations of PaCa (7,8).
In up to 75% of the cases, the tumor is located within
pancreatic head mostly sparing the uncinate process.
Tumors in the pancreatic head often present early with
biliary obstruction. However, tumors in the body and
tail can remain asymptomatic till late in disease stage.
Surgical resection is the standard of care for treatment
but only but <10% of patients with pancreatic tumors
have resectable tumors at the time of presentation. The
criteria for unresectability include infiltration of superior
mesenteric artery (SMA) and/or celiac artery or the
presence of distant metastasis including metastatic celiac or
mediastinal lymph nodes. The size of pancreatic tumor is a
major determinant of resectability and up to 83% of tumors
≤ 20 mm are resectable compared to only 7% of tumors >
30 mm in size (9). The 5 year survival rate in patients with resectable tumors can be as high as 20-25% and compares
favorably with patients with unresectable tumor, very few of
whom survive 5 years after diagnosis. Imaging techniques
currently used for diagnosis and preoperative staging of
pancreatic cancer include abdominal ultrasound (US),
contrast-enhanced computed tomography(CT), magnetic
resonance imaging (MRI), MR cholangiopancreatography
(MRCP) and invasive imaging modalities like endoscopic
retrograde cholangiopancreatography (ERCP) and
endoscopic ultrasound (EUS).
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Imaging Modalities
Abdominal Ultrasound (US)
Abdominal ultrasound (US) is widely available, noninvasive,
relatively inexpensive imaging modality without
contrast associated adverse effects. It is usually performed
to rule out choledocholithiasis and look for biliary dilation
in patients who present with jaundice and abdominal pain.
The real world accuracy of conventional US for diagnosing
pancreatic tumors is 50 to 70% (10). The results of US
are highly operator dependant. In addition, body habitus
(adipose tissue), overlying bowel gas and patient discomfort
can limit the use of US in evaluating the pancreas. If an
initial US excludes choledocholithiasis in a patient with
signs and symptoms to suggest a pancreatic etiology, CT or
MRI is commonly used for further evaluation.
Computerized Tomography (CT)
Computerized tomography (CT) is the initial
comprehensive imaging done in patients with suspected
PaCa. Since the past decade, advances in CT technology
have improved its accuracy in diagnosing and tumor staging
of PaCa.
Non-contrast CT
Ideally, use of non-contrast CT to evaluate pancreas is
limited to patients with renal failure or allergic reactions
to iodinated contrast agent used. As the pancreatic tumors
are hypovascular and can be visualized only with contrast
imaging, non-contrast CT scans have poor sensitivity and
specificity for pancreatic tumors and hence cannot be relied
on to make a diagnosis.
CT with Intravenous (IV) contrast
Multidetector CT (MDCT) provides very thin slice cuts,
higher image resolution and faster image acquisition. This
technique allows better visualization of the pancreatic
adenocarcinoma in relation to the SMA, celiac axis, superior mesenteric vein (SMV), and portal vein as greater
parenchymal, arterial, and portal venous enhancement is
achieved when imaging the pancreas with MDCT. This
can potentially aid in early detection and accurate staging
of pancreatic carcinoma (11,12). MDCT with intravenous
contrast is, therefore, generally considered as the imaging
procedure of choice for initial evaluation of most patients
suspected to have pancreatic cancer (13). It has reported
sensitivity between 76%-92% for diagnosing pancreatic
cancer (14-18). Pancreatic ductal adenocarcinoma is
hypovascular and therefore enhances poorly compared
to the surrounding pancreatic parenchyma in the early
phase of dynamic CT and gradually enhances with delayed
images. As a result, on contrast enhanced CT, pancreatic
adenocarcinoma is typically seen as a hypoattenuating area
but may occasionally be isoattenuating to the surrounding
normal parenchyma thereby leading to misdiagnosis.
Prokesch et al have reported that indirect signs such as
mass effect on the pancreatic parenchyma, atrophic distal
parenchyma, and abrupt cut off of the pancreatic duct PD
dilation (interrupted duct sign) are important and should
be considered as indicators of tumors when mass cannot
be clearly identified on CT (19). Multiple studies have
reported extrahepatic biliary dilation and/or PD dilation
(double duct sign) as findings suggestive of PaCa (20). It is
also important to be aware of changes to the parenchyma
caused by chronic pancreatitis as they can closely mimic
the changes due to PaCa and may lead to misdiagnosis.
Contrast enhanced MDCT can be used to evaluate local
extension, invasion of adjacent vascular structures and
surgical resectability with an accuracy of 80 to 90% (21).
However for pre-operative staging, it is limited in detecting
liver metastases and early lymph node metastasis (22,23).
The absolute contra-indications of contrast CT are in
patients with renal failure and contrast allergy.
Pancreatic protocol CT (CT angiography)
Preoperative staging and assessment of resectability
is usually performed using pancreatic protocol CT or
CT angiography. CT angiography is done by bolus
administration of iodinated nonionic contrast with imaging
done in arterial and venous phases after intravenous
injection of contrast. The arterial phase of enhancement,
which corresponds to the first 30 seconds after the start of
the contrast injection, provides excellent opacification of the
celiac axis, superior mesenteric artery, and peripancreatic
arteries. The portal venous phase, which is obtained at
60 to 70 seconds after the start of the contrast injection,
provides better enhancement of the superior mesenteric
vein, splenic and portal veins as well as the pancreas itself
and any liver metastases that may be present. Even though pancreatic protocol CT is widely regarded to be superior to
non-pancreatic protocol contrast MDCT for determining
resectability, there is currently insufficient direct evidence
to support this.
Magnetic Resonance Imaging (MRI) and Magnetic
Resonance Cholangiopancreatography (MRCP)
Magnetic resonance imaging (MRI) can be used in
imaging for PaCa in patients with equivocal findings at
ultrasound or MDCT. MRI examination of the pancreas
is done with intravenous administration of contrast
material and gadolinium is the most commonly used
agent. PaCa is hypointense on gadolinium-enhanced T1-
weighted images in the pancreatic and venous phases
because it is hypovascular with abundant fibrous stroma
compared to the pancreatic parenchyma. Tumors appear
isointense on delayed images because of slow wash-in of
contrast medium. MRI is commonly used to detect PaCa
when a mass lesion is not identifiable on CT scan. There is
however no significant diagnostic advantage of MRI over
contrast- enhanced CT (sensitivity of 86% on CT vs. 84%
on MRI) (24). Combining the two tests does not improve
upon what is achieved with one test alone. MRI is better at
characterizing cystic lesions of the pancreas and can provide
some indirect radiological evidence to aid in diagnosis
of pancreatic cancer. The choice of MRI or CT usually
depends upon available local expertise and the clinician’s
comfort with one or the other radio-imaging technique. It
is contraindicated in patients with metal in the body (e.g.:
pacemakers, implants) and contrast allergy.
Magnetic resonance cholangiopancreatography (MRCP)
is a useful adjunct to other radiographic diagnostic
techniques and may emerge as the preoperative imaging
procedure of choice for patients with suspected PaCa.
MRCP uses magnetic resonance technology to create a
three dimensional image of the pancreaticobiliary tree,
liver parenchyma, and vascular structures. MRCP is better
than CT for defining the anatomy of the biliary tree and
pancreatic duct, has the capability to evaluate the bile ducts
both above and below a stricture, and can also identify
intrahepatic mass lesions. It is reportedly as sensitive
as ERCP in detecting pancreatic cancers and unlike
conventional ERCP, does not require contrast material
to be administered into the ductal system (25). Thus, the
morbidity associated with endoscopic procedures and
contrast administration is avoided. Although MRCP has not
yet completely replaced ERCP in patients with suspected
pancreatic cancer in all centers, it is routinely used in
patients with high grade stenosis of the gastric outlet or
proximal duodenum or in those with certain post-surgical anatomy (e.g., Billroth II, Roux-en Y biliary bypass), which
make the biliary ductal system difficult to access by ERCP
(26). Chronic pancreatitis can be difficult to differentiate
from pancreatic adenocarcinoma on MRI since both show
low signal intensity on T1-weighted images and both
may be associated with pancreatic and/or biliary ductal
obstruction. Dynamic gadolinium-enhanced MRI cannot
differentiate chronic pancreatitis and PaCa on the basis
of degree and time of enhancement (27). MRCP images
may be more helpful in distinguishing between chronic
pancreatitis and pancreatic adenocarcinoma especially if
the duct-penetrating sign signifying a non-obstructed main
pancreatic duct is present (28).
Positron Emission Tomography (PET) Imaging
Positron emission tomography(PET) scanning with the
tracer 18-fluorodeoxyglucose (FDG) relies upon functional
activity to differentiate metabolically active proliferative
lesions such as cancers, most of which are FDG-avid lesion
such as cancers from benign lesions, most of which do
not accumulate FDG with the exception of inflammatory
lesions such as chronic pancreatitis. The utility of PET
in the diagnostic and staging evaluation of suspected
PaCa remains uncertain and there is still no consensus on
whether PET provides information beyond that obtained
by contrast-enhanced CT (29). As PET imaging is usually
performed after the initial CT, the sensitivity and specificity
of PET varied depending on the CT result. Sensitivity and
specificity after a positive CT was 92% (87 to 95) and 68%
(51 to 81); after a negative CT, the corresponding values
were 73% (50 to 88) and 86% (75 to 93). Elevated serum
blood glucose levels increase the number of false negative
PET scans. Data published on the use of PET scans in PaCa
are conflicting. Some studies suggest that PET is useful for
identifying metastatic disease that is missed by CT (30),
while others reported that PET often misses small volume
metastases within the peritoneum and elsewhere, including
the liver (31).
More recent studies have investigated the value of
integrated PET/CT, which has better spatial resolution as
compared to PET scans. In one case series, the sensitivity
and specificity of PET/CT for the diagnosis of PaCa
compared with CT alone was 89% versus 93% and 69%
versus 21% respectively (32). PET/CT is also superior to
conventional imaging (MDCT, CT angiography, EUS)
used for tumor staging and detection of distant metastases
(sensitivity and specificity rates were 89 versus 56 and
100 versus 95 percent, respectively). A major limitation
of this study was that the CT component of PET/CT was
performed without the use of intravenous contrast material. When compared to MDCT with contrast, currently
available data does not show that PET or integrated PET/
CT provide any additional information. Further studies are
needed to evaluate the role of PET for diagnosis and staging
especially in patients with a negative or indeterminate
MDCT.
Endoscopic Retrograde Cholangiopancreatography (ERCP)
Endoscopic Retrograde Cholangiopancreatography
(ERCP) is used for diagnosis and palliation in patients with
known or suspected pancreatobiliary malignancies. During
an ERCP, cannula is passed from the endoscope into the
pancreatic or biliary ducts. Contrast dye is injected through
the cannula into the ducts and the biliary and pancreatic
ductal systems are visualized flouroscopically. In contrast
to other imaging modalities, tissue diagnosis of the involved
ducts may be achieved using needle aspiration, brush
cytology, and forceps biopsy. Brush cytology has 35-70%
sensitivity and 90% specificity (33). Triple sampling using
brush cytology, FNA and forceps biopsy of biliary stricture
during ERCP improves the sensitivity for diagnosing cancer
to 77% (34). ERCP and brushing of biliary stricture has
better diagnostic accuracy for cholangiocarcinoma (about
80%) compared to pancreatic carcinoma (35). ERCP has a
limited role in staging of pancreatic and biliary cancers.
Palliation of biliar y obstruction in patients with
pancreatic and biliary cancer may be performed with
biliary stent placement with ERCP or a surgical bypass.
The available evidence does not indicate a major advantage
to either alternative, so the choice may be made depending
on clinical availability and patient or practitioner
preference. ERCP is a widely available imaging modality
and this modality may be preferable to surgery in some
cases due to lower overall resource utilization and shorter
hospitalization. The role of ERCP in biliary drainage prior
to surgery for potentially resectable pancreatic cancers
is currently debated and should be individualized based
on specific clinical situation. However, the vast majority
of patients with PaCa has an unresectable or borderline
resectable tumor requiring chemotherapy ± radiation and
would benefit from an ERCP for biliary drainage. Acute
Pancreatitis is a side effect encountered after ERCP in 5-7%
of the patients. Gastrointestinal bleeding, perforation,
infection and sore throat are other less common
complications of ERCP.
Endoscopic Ultrasound Guided Fine Needle Aspiration
(EUS/EUS-FNA)
EUS/EUS-FNA is used for definitive diagnosis of PaCa or in patients with suspected cancer not diagnosed by
conventional imaging. EUS examinations are usually
performed using radial echoendoscope initially and
whenever a suspicious ‘mass’ lesion is identified during
the EUS exam, fine needle aspiration (FNA) is performed
using a linear echoendoscope. Fine needle passes are
made using a EUS-FNA needle in the same sitting. The
cytology specimens are usually stained by the Diff-Quik
and Papanicoulou method (Pap smear) and sample is
collected for cell blocks. The final diagnosis is based on
examination of the Pap smears and the cell blocks using
standard cytologic criteria (36). Special cytology stains
are used as indicated to diagnose neuroendocrine tumors.
The sensitivity of EUS-FNA for diagnosing pancreatic
cancer has ranged from 80-95% in various published studies
(37-39). The performance characteristics of EUS-FNA
for diagnosing PaCa seem to be inf luenced by presence
of obstructive jaundice at initial clinical presentation and
presence of underlying chronic pancreatitis. In patients
without obstructive jaundice, the diagnostic accuracy of
EUS-FNA is very high (98.3%) and is not significantly
influenced by presence of underlying chronic pancreatitis.
However, in patients presenting with obstructive jaundice,
the sensitivity(92.0%) and accuracy(92.5%) of EUS-FNA
for diagnosing malignancy is significantly lower especially
so in patients with chronic pancreatitis (40). Absence
of an identifiable mass lesion on EUS rules out PaCa
with almost 100% certainty in the hands of experienced
endosonographers (41). The accuracy of EUS-FNA for PaCa
diagnosis can be further improved with use of adjunctive
immunostaining in slides obtained by smearing EUS-FNA
specimens (42). EUS is helpful in further evaluation of
patients with non-specific and subtle findings suggestive of
PaCa on CT and MRI imaging. We had earlier reported in
non-jaundiced patients with “enlarged head of pancreas” or
“dilated PD with or without a dilated CBD” on CT/MRI, a
pancreatic malignancy was present in 9.0% of patients and
EUS-FNA diagnosed cancer in these patients with 99.1%
accuracy (43).
EUS probably has a role in preoperative staging of PaCa
for determining resectability. Portal vein and splenic vein
invasion are visualized better with EUS. However, tumor
involvement of SMA and SMV is not reliably determined
by EUS. In published studies , EUS has a T-stage accuracy
of 78-94% and N-stage accuracy of 64-82% (44-49).
However, the presence of biliary stent at the time of EUS
examination reduced the T-stage accuracy to 72% (50). EUS
also plays a role in identification and biopsy of metastatic
peripancreatic, celiac and mediastinal lymph nodes for
tumor involvement. Ahmed et al., questioned the role of
EUS for T-staging and found its accuracy between 49% and 69% in two different studies (51,52). With recent advances
in CT and MRI technology and the ability to perform
image reconstruction, very detailed evaluation of vascular
infiltration by tumors is nowpossible. EUS imaging probably
has an adjunctive role in T-staging of pancreatic tumors.
However, due to its ability to reliably identify lymph nodal
metastasis in celiac and mediastinal lymph nodes, EUSFNA
can prove to be beneficial in pre-operative assessment
of resectability (53,54). The main limitation of EUS is its
operator dependence and limited availability of expert
endosonographers for accurate reporting. EUS carries a
0.1-1% risk of pancreatitis. As with any invasive procedure,
complications like bleeding, tear, anesthetic complications
can occur but are rare.
In conclusion, MDCT is the preferred initial imaging
modality in patients with clinical suspicion for pancreatic
cancer. The role of MRI for use in pancreatic cancer
diagnosis is evolving and is currently used interchangeably
with MDCT for this purpose. MRCP seems promising in
differentiating pancreatic cancer from chronic pancreatitis.
PET scans can provide information on occult metastasis
but its clinical benefit is not established. EUS is the most
accurate examination for diagnosing pancreatic cancer
and can be a useful adjunct to CT/MRI in determining
resectability of pancreatic cancer. EUS/EUS-FNA can
also provide a definite determination about the presence
of pancreatic cancer in patients with non-specific findings
suggestive of cancer on conventional imaging.
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References
Cite this article as:
Tummala P, Junaidi O, Agarwal B. Imaging of pancreatic cancer: An overview. J Gastrointest Oncol. 2011;2(3):168-174. DOI:10.3978/j.issn.2078-6891.2011.036
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