Matas Kalinauskas1, Vaida Ruseckaitė1, Vytautas Dūdėnas1
1Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine
Abstract
Introduction
Pancreatic cancer is a neoplasm with a mortality rate, which is almost equal to its occurrence. Pancreatic adenocarcinoma is the most common malignancy with an incidence of over 90% of all pancreatic cancers. It is especially lethal, as its 5 year overall survival rate is less than 5%. However, the rate of survival is gradually increasing due to the new treatment methods and the improvement of diagnostic techniques. Endoscopic ultrasound is a diagnostic method with the highest sensitivity, when detecting malignant pancreatic lesions.Aim
To review scientific literature and determine the benefits and drawbacks of endoscopic ultrasound in diagnosing and treating pancreatic cancer.
Materials and methods
Literature analysis. A research articles in English language on the “PubMed” 2010 to 2019 database. Keywords used in the search: “Endoscopic ultrasound”, “Pancreatic cancer”.
Results
Endoscopic ultrasound becomes the first choice method, when it comes to diagnosing small pancreatic tumors (<3cm), overlapping computer tomography and multi-detector-row computer tomography with EUS presenting a higher sensitivity (87%) and accuracy (92%) in detecting pancreatic tumors than MDCT. Furthermore, EUS plays a crucial role in diagnosis of small focal lesions and tumors with the help of EUS guided fine needle aspiration biopsy. Also, EUS guided FNA should be used in the preoperative examination of patients with pancreatic neoplasms. Moreover, EUS can be used as a palliative pain treatment for patients with PC with celiac plexus/ ganglion neurolysis.
Conclusions: many studies agree that EUS is a valuable tool in the diagnosis and treatment of pancreatic cancer and should be used in practice more often than not. The main drawbacks are its availability due to the price and personnel required.
Keywords: Endoscopic ultrasound, pancreatic cancer
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Medical Sciences 2020 Vol. 8 (14), p. 29-34
Endoscopic Ultrasound in the Diagnosis of Pancreatic Cancer
Matas Kalinauskas
1
, Vaida Ruseckaitė
1
, Vytautas Dūdėnas
1
1
Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine
Abstract
Introduction
Pancreatic cancer is a neoplasm with a mortality rate, which is almost equal to its occurrence. Pancreatic adenocarcinoma is the most
common malignancy with an incidence of over 90% of all pancreatic cancers. It is especially lethal, as its 5 year overall survival rate
is less than 5%. However, the rate of survival is gradually increasing due to the new treatment methods and the improvement of
diagnostic techniques. Endoscopic ultrasound is a diagnostic method with the highest sensitivity, when detecting malignant pancreatic
lesions.Aim
To review scientific literature and determine the benefits and drawbacks of endoscopic ultrasound in diagnosing and treating
pancreatic cancer.
Materials and methods
Literature analysis. A research articles in English language on the "PubMed" 2010 to 2019 database. Keywords used in the search:
“Endoscopic ultrasound”, “Pancreatic cancer”.
Results
Endoscopic ultrasound becomes the first choice method, when it comes to diagnosing small pancreatic tumors (<3cm), overlapping
computer tomography and multi-detector-row computer tomography with EUS presenting a higher sensitivity (87%) and accuracy
(92%) in detecting pancreatic tumors than MDCT. Furthermore, EUS plays a crucial role in diagnosis of small focal lesions and
tumors with the help of EUS guided fine needle aspiration biopsy. Also, EUS guided FNA should be used in the preoperative
examination of patients with pancreatic neoplasms. Moreover, EUS can be used as a palliative pain treatment for patients with PC
with celiac plexus/ ganglion neurolysis.
Conclusions: many studies agree that EUS is a valuable tool in the diagnosis and treatment of pancreatic cancer and should be used in
practice more often than not. The main drawbacks are its availability due to the price and personnel required.
Keywords: Endoscopic ultrasound, pancreatic cancer.
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30
List of abbreviations
PC -pancreatic cancer
PDAC - pancreatic ductal adenocarcinoma
EUS - endoscopic ultrasound
FNA - fine needle aspiration
US - ultrasonography
CT - computer tomography
MRI- magnetic resonance tomography
MRCP - magnetic resonance cholangiopancreatography
MDCT - multi-detector-row computer tomography
CE-EUS - contrast – enhanced endoscopic ultrasound
CPN - celiac plexus neurolysis
CGN - celiac ganglion neurolysis
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Introduction
Pancreatic cancer is a neoplasm with a mortality rate, which
is almost equal to its occurrence. Pancreatic adenocarcinoma
is the most common malignancy with an incidence of over
90% of all pancreatic cancers. It is especially lethal, as its 5
year overall survival rate is less than 5%. However, the rate
of survival is gradually increasing due to the new treatment
methods and the improvement of diagnostic techniques. [1,
2] For the previously mentioned characteristics of PC, early
diagnosis is essential. Endoscopic ultrasound is a diagnostic
method with the highest sensitivity, when detecting
malignant pancreatic lesions. [3] EUS guided fine needle
aspiration is especially useful for the differential diagnosis
of PC or when a histopathological evaluation is needed. [1]
What is more, EUS is also a helpful tool for preoperative
staging of PC. [4] In this study we seek to evaluate the
advantages of each available diagnostic tool in detection of
PC. We also aim to compare EUS with traditional
radiological screening methods – ultrasonography,
computed tomography and magnetic resonance tomography.
Results
Ultrasonography
Ultrasonography (US) is usually performed as a first – line
imaging modality on patients with PC. It is also performed
on asymptomatic patients as painless, cost – effective
screening method. The frequency of US has also increased
and it has a significant role in the detection of PC. US is a
great imaging method in terms of its low – cost and non –
invasiveness. Recent studies have also shown that early
diagnosed PC had mostly UG findings, such pancreatic cysts
or dilated pancreatic ducts. However, US is highly
dependent on the skills of the examiner and requires a lot of
experience in order to diagnose accurately. The sensitivity
of US is 75 – 89% and specificity 90 – 99%. [20] As
mentioned before, it is dependent on the experience of the
examiner, the patient´s body mass, gas in the bowels and the
topography of the pancreas. In order to obtain better
visualization of the pancreas, US should be performed on
multiple planes – longitudinal, transverse and oblique. It is
also suggested that the patient should only eat a light meal
on the evening before the procedure and
refrain himself from eating on the morning of the procedure.
This reduces the amount of gas in the bowels. It is also
important to use multiple methods to improve the
visualization of the pancreas during US. For example, ask
the patient to hold his breath during inspiration or
expiration, change the position into Fowler´s, where the
hands of the patient are placed behind his back and apply
more pressure on the abdominal wall with the transducer. In
some cases, the liquid – filled stomach method can also be
used. When using this method, the patient is required to
drink up to 300 ml of still water. This helps to create a
gastric sonic window by pushing the gas to the fundus of the
stomach. This method should not be used on patients, who
have undergone gastric surgery, as the fluid does not remain
in the correct anatomical location. When detecting a small
pancreatic cyst or a lesion, a high – frequency transducer
can be used. In this case, it is important to change the
patient´s position and to suspend breathing during
inspiration or expiration. [9]
Computer Tomography
Abdominal computer tomography is one of the methods
used for initial screening once clinical signs of pancreatic
cancer manifest. The goal of screening is to determine the
presence of a malignancy in the pancreas and evaluate if it is
resectable. Typically an ill-defined, hypoattenuated mass in
the pancreas is seen. Smaller lesions tend to be
isoattenuating, which makes diagnosis difficult. Secondary
signs are pancreatic duct cut off or dilatation, dilatation of
common bile duct, contour abnormalities and parenchymal
atrophy. If both the pancreatic and the common bile duct are
dilated, it is called a double duct sign, which is present in
62% to 77% cases of pancreatic cancer, but is not a
diagnostic sign, as benign adenomas and autoimmune
pancreatitis may display it as well [16]. If the tumor is
sizeable enough, an enlargement of the whole pancreas can
be observed. Sensitivity of computed tomography depends
on the chosen technique and size of tumor (lesions that are
<2cm in diameter have a low sensitivity). The highest
sensitivity technique is triple-phase contrast-enhanced thin-
slice helical computed tomography, known as MDCT [17].
This technique allows the imaging of larger volumes of
tissue and acquiring venous and arterial phases in a shorter
time period. This allows evaluating vascular involvement in
the tumor, which is an important factor when determining
operability [5].
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A so-called pancreas protocol is used when pancreatic
cancer is suspected, which consists of scanning a patient in 3
dynamic phases of contrast injection. 1) The first 30 seconds
after injection, called the arterial phase. Peripancreatic
arteries and superior mesenteric artery are evaluated during
this phase. 2) A period between peak enhancement of the
aorta and peak enhancement of the liver is called the
pancreatic phase. During this phase, the difference between
healthy pancreas tissue and tumor tissue is most
conspicuous. 3) 60-70 seconds after injection, the portal
venous phase occurs. During this time splenic, portal and
superior mesenteric veins can be evaluated. Due to peak
liver enhancement, it is also an optimal time to evaluate the
liver for metastases. [15]
Screening Methods of Pancreatic Cancer
For people with high risk of pancreatic cancer (this includes
mutation carriers of PDAC-prone gene mutations, for
example: CDKN2A, BRCA1, BRCA 2, STK11/LKB1 and
relatives of patients with familial pancreatic ductal
adenocarcinoma (PDAC)) there are no clear screening
guidelines yet, or when surgical treatment may come in to
play.[9] MRI and MRCP both are able to detect small
pancreatic and pancreatic duct abnormalities, mostly of
cystic origin and they also have a better visualization of the
soft tissue of pancreas than CT.[8] When it comes to the
question whether we should use EUS or MRI for early
diagnosis of PC, there aren’t a lot of studies made that
compare these methods directly. Several studies have been
done comparing the sensitivity using CT, MRI and EUS for
pancreatic lesions in patients with high risk of PC. All the
individuals chosen for this study underwent CT, MRI and
EUS screening and of 216 patients 96 were identified with a
minimum of one pancreatic mass/lesion (84 were found
cystic and 3 solid) by at least one imaging method. CT
detected 11%, MRI 33,3% and EUS 42,6% of pancreatic
lesion for these patients.[9,14] For detecting malignancies in
the pancreas smaller than 30mm in diameter the results of
sensitivities of all three methods were given: CT - 53%,
MRI - 67%, EUS - 93%. However, for local liver metastasis
EUS imaging was found not accurate enough mostly
because of the limited anatomical view of the liver and both
CT and MRI were found better in this case.[19] Another
recent study was done comparing EUS and MRI for high-
risk individual screening of pancreatic lesions. It concluded
that both modalities are important in detecting early
pancreatic abnormalities. MRI has 89% sensitivity in
visualizing cystic lesions of any size compared to EUS 38%.
However, EUS had a 100% sensitivity for imaging solid
lesions, whereas MRI 0% was found redundant. The
concluding results of the study stated that both methods
EUS and MRI were integral in screening of high-risk
individuals, rather than one being superior to another.[18]
Both MRI and EUS are superior to CT in early screening of
high-risk individuals, but when to choose one over the other
is still unclear. MRI may be a non-invasive method, that can
accurately detect other extrapancreatic masses and has a
high sensitivity for visualizing cystic lesions, but for some
patients it may be difficult to do this test due to
claustrophobia. Also, if a lesion is spotted on MRI imaging
it could require further investigation and even a biopsy with
EUS-FNA for confirmation of a malignant process. On the
other hand, with EUS the biopsy can be done with a single
procedure. Furthermore, EUS has a superior ability to detect
small <30mm tumors and solid masses in the pancreas.
However, EUS can be discomforting for patients because it
is an invasive procedure. It requires anesthesia so there is a
higher risk of anesthesia related complications. Also, the
sensitivity of the method relies a lot on the experience of the
operator. Having taken this into account, as mentioned
before no clear guidelines are available for physicians,
therefore, studies suggest that both EUS and MRI together
must be considered for screening for high risk
individuals.[14]
Capabilities of Endoscopic Ultrasound
EUS examination is done under general anesthesia. Most
times the patient is lied down on his left side in the
decubitus position. The ultrasound probe can be placed
either by the patient’s head or feet. [1]
EUS is considered as a far better method than a
conventional CT, when diagnosing PC. Although CT can be
used to visualize a large mass or lesion around the pancreas,
EUS has a higher sensitivity and specificity when
indentifying small tumors that cannot be seen by other
imaging modalities and is more sensitive for early cancer
detection [3, 5]. Studies have been made comparing multi-
detector-row CT (MDCT)and EUS for PC diagnosis.
Research concluded that EUS presented a higher sensitivity
(87%) and accuracy (92%) in detecting pancreatic tumors
than MDCT. Furthermore, the accuracy of diagnosing PC
can be increased by using contrast – enhanced harmonic
EUS. The basic principle of this method is that CE-EUS
helps visualize the vascularity and blood flow of the lesion
which is located in the pancreatic parenchyma. Intravenous
injection of contrast material during a conventional EUS
session can help differentiate inflammatory process from a
malignant tumor. It is extremely helpful in visualizing
pancreatic adenocarcinomas which usually remain
hypoechogenic, while other neoplasms or inflammatory
lesions are isoechogenic or hyperechogenic. Studies
confirmed, that using contrast material during EUS when
detecting pancreatic adenocarcinomas the sensitivity was
94% and specificity was 89%. However, CE-EUS is limited
by its high contrasting agent cost and shortage of
professionals, who expertise in this area. [1, 3, 6, 7]
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Furthermore, the role of EUS is crucial, when a patient is
confirmed with atypical parenchymal changes in the
pancreas. For example: enlargement of the pancreatic
gland, dilatation of pancreatic ducts with no obstruction to
be seen. For these cases, if needed, a biopsy by FNA can be
taken. EUS - guided FNA is extremely accurate for
diagnosing focal lesions and small tumors, which are less
than 3 cm. Some of the indications for EUS – guided FNA
are: planning palliative, adjuvant or neoadjuvant
chemotherapy for unresectable pancreatic lesions; to
confirm the diagnosis of pancreatic adenocarcinomas or
other tumor before a radical treatment; differential diagnosis
from inflammatory pseudotumor or a fibrous nodule. [1,3,5]
Also, EUS-FNA has a sensitivity of 96,7% and specificity of
100% for diagnosing para-aortic lymph node metastasis,
which is considered as one of the contraindications for
surgical treatment, concluding that EUS-guided FNA should
be included in the preoperative examination of patients with
pancreatic neoplasms. [8] The accuracy of EUS – guided
FNA for pancreatic lesions varies between 87%-95.8%. [5]
EUS is also superior compared to CT for tumor staging.
Studies show, that T staging sensitivity and specificity is
between 72%-90% and 87% for vascular invasion, whereas
CT staging is 30% and 55% respectively. The staging for N
by EUS shows accuracy of 50%-86%. [4, 8, 9]
Moreover, EUS can be used as a palliative pain treatment
for patients with PC. An acceptable method is EUS – guided
celiac plexus neurolysis/block using alcohol or phenol. The
substance is injected into or around the celiac plexus or
ganglion. EUS provides a better pathway and allows to
avoid vessels, which you could damage using a
percutaneous approach. Most PC patients require morphine
or other narcotic analgesia, which may cause dependency
and other systemic malfunctions overtime. Studies show,
that patients with CPN procedures tend to consume less
narcotic analgesia than people without the procedure.
Furthermore, celiac ganglion neurolysis showed better pain
management results than celiac plexus neurolysis: CGN
73.5% vs CPN 45.5%. [10, 11]. Also, for patients with
unresectable PC radiotherapy, more particularly
brachytherapy, guided with EUS can be used. A study has
been made using Iodine-125 radioactive seed, which was
placed inside the malignant lesion for local cell destruction.
The results of the trial showed that from a total of 15
patients 27% responded partially to treatment, 20% had only
minimal response, and in 33% of patients the treatment
didn’t work at all. Although, 30% of patients expressed a
mild diminishment in symptoms, more particularly pain, but
the effect was not long lasting. There were, however, three
patients who experienced adverse (pancreatitis, pseudocyst
formations) local effects and three patients who experienced
systematic adverse effects (hematologic toxicity). The
results concluded that a study of EUS guided brachytherapy
alongside systemic chemotherapy in patients with
unresectable PC could give better results than radiotherapy
alone. These studies were made, but a significant
improvement on survival rates was not achieved, only
moderate correction of pain was prominent. [10]
Discussion
The use of EUS in the diagnosis and treatment of pancreatic
cancer has been growing more wide-spread in the recent
years. Many studies agree that its use is important in both
the initial diagnosis and preoperative staging, mainly in the
evaluation of vascular invasion of the portal vein and vessels
of the spleen, as well as in the treatment of pain via CPN
[11, 12]. This is especially true for the diagnosis of small
(<5mm) solid tumors, unresectable pancreatic lesions and
metastases, which are not available to transcutaneous
biopsy. EUS is also valuable in the differential diagnosis
between fibrous and inflammatory nodules, when the
histology result of the lesion is doubtful. EUS and MRI are
the most valuable imaging modalities in the diagnosis of PC.
What is more, EUS has a major advantage, compared to
MRI - it is valuable in aiding FNA procedures, which allow
doctors to evaluate both the local tumor (T) and lymph
nodes (N). The advantages of EUS over CT are lack of
ionizing radiation and higher sensitivity and specificity. It
does, however, have drawbacks, as it is an invasive
procedure that often requires anesthesia, highly trained
physicians with specialized knowledge. The advancement of
cross – sectional imaging techniques, such as helical CT, has
greatly reduced the use of EUS in the staging and
diagnostics of PC. [13] Due to these reasons and the fact
that PC has a low incidence in the general population (<1%),
it is not advised to use EUS as a screening method. The
exception would be patients with confirmed familial
pancreatic cancer. [14]
Conclusion
US is the optimal tool for initial screening of PC due to its
safety and availability. It is however too highly dependent
on the operators skill. CT is highly sensitive if proper
screening modalities are used. This makes it a good tool for
following up of known patients, but ineffective for initial
screening. MRI is the most sensitive of traditional
radiological methods. It is however incapable of detecting
solid lesions in the pancreas. Using EUS in combination
with MRI is the best available option for detecting
pancreatic cancer. Many studies agree that EUS is a
valuable tool in the diagnosis and treatment of pancreatic
cancer. The main drawbacks are its availability due to the
price and personnel required. However, due to its higher
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34
sensitivity and specificity than CT, it should be used
whenever available in the initial diagnosis and staging of
PC.
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