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Endoscopic Ultrasound in the Diagnosis and Staging of Pancreatic Cancer

Endoscopic Ultrasound in the Diagnosis and Staging of Pancreatic Cancer

Endoscopic ultrasound was developed in the early 1980s
to overcome the limitations of transabdominal ultrasound in imaging the
gastrointestinal wall and retroperitoneum.[1] The ultrasound transducer
(positioned at the endoscope tip) is applied directly against the duodenal or
gastric wall. This enhances the image quality by minimizing intervening adipose
tissue and air that must be traversed by the ultrasound. The proximity of the
transducer to the target tissue allows the use of higher frequency ultrasound
and leads to greater image resolution. Accordingly, the use of endoscopic
ultrasound has become routine for diagnosing and staging pancreatic and other
gastrointestinal tumors.[2-4]

Dedicated Instruments

Two types of dedicated instruments are available with which to perform
endoscopic ultrasound—each has different properties that offer unique
advantages and disadvantages. For both instruments, acoustic coupling is
achieved by filling either the intestinal lumen or a balloon attached to the tip
of the endoscope with water. An oblique forward-viewing fiber or video optic
system is used to help direct instrument passage.

The most commonly used instrument is the radial echoendoscope, which has a
mechanically rotating transducer that provides a 360-degree transverse image.
This image is in a plane perpendicular to the longitudinal axis of the endoscope.
The complete scanning arc and the radial orientation of the image simplify
structure recognition. Operating from 7.5 to 20 MHz, the transducer can be
easily switched from one frequency to another during the endoscopic ultrasound
examination, thus modifying the depth of penetration and image resolution.

A linear echoendoscope, equipped with an electronic array transducer that
produces a sagittal image parallel to the longitudinal axis of the endoscope, is
also available. Operating at 5 and 7.5 MHz, this instrument allows continuous
real-time imaging and guidance of a 19- or 22-gauge needle as it is passed from
the endoscope into a lesion. This feature allows one to perform fine-needle
aspiration (FNA) of peri-intestinal tumors, lymph nodes, and fluid collections.
In a similar fashion, therapeutic interventions such as celiac plexus neurolysis
and pseudocyst draining may be achieved. Doppler and color Doppler are available
and are used to identify vascular structures.

Detection of Pancreatic Tumors

Extensive data indicate that endoscopic ultrasound is a highly sensitive
method for identifying pancreatic neoplasms, with detection rates greater than
90% (Table 1).[2,5-12] In most studies, endoscopic ultrasound has proven
superior to transabdominal ultrasound, computed tomography (CT), endoscopic
retrograde cholangiopancreatography (ERCP), and angiography in the detection of
pancreatic tumors.[2,6,12-14]

In a study by Rosch and colleagues, endoscopic ultrasound demonstrated
greater sensitivity (99%) and specificity (100%) than abdominal ultrasound
(sensitivity: 67%, specificity: 40%) and CT scan (sensitivity: 77%, specificity:
53%) for detecting pancreatic tumors.[2] Recent studies comparing endoscopic
ultrasound with helical CT, magnetic resonance imaging (MRI), and
positron-emission tomography have found endoscopic ultrasound to have a greater
sensitivity for identifying pancreatic neoplasms.[5,7,11,15] In another study of
34 patients with elevated levels of CA 19-9 and a normal pancreas according to
transabdominal ultrasound and CT scan, endoscopic ultrasound was 94% accurate in
detecting a pancreatic or biliary neoplasm, with a positive and negative
predictive value of 92% and 100%, respectively.[16]

The advantage of endoscopic ultrasound is even greater for recognizing tumors
that are less than 2 to 3 cm in diameter.[2,7,12,17,18] For pancreatic tumors
less than 2 cm, Yasuda and colleagues found that endoscopic ultrasound had a
detection rate of 100% (ERCP: 57%, transabdominal ultrasound: 29%, CT: 29%, and
angiography: 14%).[12] In another study by Rosch and associates, the diagnostic
sensitivity of endoscopic ultrasound for detecting tumors smaller than 3 cm was
100%, compared with 57% for transabdominal ultrasound and 68% for CT.[19]

Neuroendocrine Pancreatic Tumors

Endocrine tumors of the pancreas are rare, with a prevalence of less than 1
per 100,000 persons.[20] Insulinoma, gastrinoma, and nonfunctioning tumor are
most common, while glucagonoma, somatostatinoma, and vipoma are less often
reported (Figure 1). Resection offers the only chance for cure and should be
undertaken whenever possible due to the malignant potential of these tumors.

Preoperative determination of the tumor’s location and extent is necessary
to enable the surgeon to plan the optimal surgical approach. Preoperative
localization is also important because it is difficult to locate these tumors
during surgery in up to 20% of insulinomas and as many as 50% of gastrinomas.[20]
Efforts at tumor localization should be reserved for patients in whom
biochemical studies support the clinical diagnosis of a pancreatic
neuroendocrine tumor and not as part of a screening examination.[21]

The approach to tumor localization is similar for all tumor types. Various
imaging modalities are available for preoperative identification of pancreatic
endocrine tumors. They include transabdominal ultrasound, CT, selective
abdominal angiography, selective venous sampling, radiolabeled somatostatin
analog (octreotide)-receptor scintigraphy (SRS), intraoperative ultrasound, and,
most recently, endoscopic ultrasound.

Insulinomas

Endoscopic ultrasound is increasingly being used in the diagnostic evaluation
of endocrine tumors of the pancreas because of its ability to identify small
lesions (Figure 2). Studies report a localization rate of approximately 77% to
93% for insulinomas.[4,20,22-27] In these same studies, CT was able to locate
the tumor in 0% to 20% of patients, and SRS in only 12% to 14%. Insulinomas have
a low density of somatostatin receptors and as a result often go undetected by
SRS. The high detection rate of endoscopic ultrasound for insulinomas is likely
explained by the fact that 99% of insulinomas are confined to the
pancreas.[25,28,29]

Gastrinomas

About 75% to 100% of pancreatic gastrinomas are localized by endoscopic
ultrasound,[4,20,22,25,26,30] but only 0% to 67% of duodenal gastrinomas can be
identified.[20,22,26] Endoscopic ultrasound is comparable to SRS for detecting
pancreatic gastrinomas, and both tests are clearly superior to CT. Even so, both
techniques may miss a significant proportion of duodenal gastrinomas.[20,22,26,31]
This is important, since as many as 30% to 45% of gastrinomas (single or
multiple lesions) are located in parapancreatic locations, most notably the
duodenal wall or lymph nodes.[28] Duodenal wall gastrinomas are commonly missed
by endoscopic ultrasound, despite special attention to this area, unless
previously identified endoscopically.[25] Therefore, the endoscopic ultrasound
examination should always be accompanied by a careful forward- and side-viewing
examination of the duodenal wall.

General Observations

Endoscopic ultrasound FNA increases the accuracy for detection of pancreatic
endocrine tumors. Accuracy rates of 75% to 80% have been reported.[21,30,32] In
addition, endoscopic ultrasound may also identify multifocal tumors not seen by
other imaging modalities.[32] In a multicenter trial involving 37 patients with
a suspected neuroendocrine pancreatic tumor undetected by transabdominal
ultrasound and CT, the sensitivity and specificity of endoscopic ultrasound for
tumor localization was 82% and 95%, respectively.[2] These tumors had a mean
diameter of 1.4 cm (range: 0.5 to 2.5 cm) and consisted of 31 insulinomas, 7
gastrinomas, and 1 glucagonoma. In this same study, only 27% of these tumors
were identified by angiography. All patients underwent surgical resection, with
36 of 37 patients considered cured based on clinical and laboratory parameters.

The endoscopic ultrasound appearance of neuroendocrine pancreatic tumors is
similar, regardless of the type of tumor. They typically appear as round,
well-delineated, homogenous, echo-poor lesions, with a surrounding hyperechoic
rim. Their appearance can vary with reports of cystic or calcified tumors,
echo-rich lesions, an echo-poor border, or echotexture similar to the
surrounding pancreatic parenchyma.[2,36,37] The endoscopic ultrasound technique
for localizing these tumors is identical to that of adenocarcinomas, except that
a more thorough examination may be needed to find these small lesions.

The parapancreatic region should also be carefully examined—not only to
search for malignant lymph nodes but to look for primary tumors as well.[17,38]
Parapancreatic tumors are more difficult to locate than intrapancreatic tumors;
they may be attached by a pedicle or completely separate from the
pancreas.[25,35] As with other tumors, infiltration into adjacent organs and
vessels should be evaluated. Endoscopic ultrasound FNA helps differentiate
benign parapancreatic lymph nodes from a primary neuroendocrine pancreatic
tumor, a distinction that may be especially difficult to make for insulinomas.[4,23-25,32,39-41]

Cost-Effectiveness

The cost-effectiveness of endoscopic ultrasound for the preoperative
localization of pancreatic endocrine tumors was recently demonstrated by Bansal
and colleagues in a case-control study. They compared the costs of performing
tumor localization with and without endoscopic ultrasound as part of the
protocol, and found that the use of endoscopic ultrasound significantly reduced
the costs of preoperative staging ($2,620 vs $4,846). The savings occurred
because of both a decrease in the number of angiograms and venous sampling
procedures performed and a reduction in surgical and anesthesia times. The cost
per tumor located was $3,144 when endoscopic ultrasound was used vs $5,628 when
it was not.

Recommendations

Endoscopic ultrasound is an accurate technique for detecting functioning
neuroendocrine pancreatic tumors. We suggest performing an endoscopic ultrasound
in all patients in whom surgery is planned; some practitioners favor its use
only when noninvasive studies detect no metastases and no primary tumor is seen.
We favor this approach even when a lesion has already been identified in order
to detect unsuspected multifocal or metastatic disease. The additional
information obtained by endoscopic ultrasound FNA allows cytologic confirmation
of the diagnosis with reduced false-positive imaging results. It also allows the
surgeon to plan the optimal strategy (ie, tumor enucleation vs pancreatic
resection). More studies are needed, however, to determine the role and utility
of endoscopic ultrasound FNA when noninvasive studies have already localized a
tumor.

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