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, somatostatin(Drug information on somatostatin)oma, 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.
A 48-year-old female presents with complaints of irregular vaginal bleeding and postcoital bleeding. Images from a PET/CT and pelvis MRI reveal characteristic findings. What is your diagnosis?
