imaging studies.47 Pancreatic polypeptide is secreted by the PP cells of the islets of Langerhans and can

also be used to track patients with PENs, though its sensitivity (63%) is lower than that of

chromogranin A.48 Neuron-specific enolase is another tumor marker that is elevated in approximately

50% of PENs, most commonly in patients with pulmonary metastases.49

PENs presenting due to mass effect on surrounding structures resulting in jaundice, pain, or gastric

outlet obstruction are uncommon. These lesions should be addressed as any other symptomatic

pancreatic lesion with definitive surgical resection if clinically appropriate.

Patients presenting with symptoms from a functional PEN can be a diagnostic challenge. Three

general principles apply to the diagnosis and treatment of patients with suspected functional neoplasms

of the endocrine pancreas. One must first recognize the abnormal physiology or characteristic

syndrome. Patients are often misdiagnosed or have their symptoms disregarded for years before an

accurate diagnosis is reached. Characteristic clinical syndromes are well described for insulinoma,

gastrinoma, VIPoma, and glucagonoma. The somatostatinoma syndrome is nonspecific, much more

difficult to recognize, and exceedingly rare. Second is the detection of hormone elevations in the serum

by radioimmunoassay. Such assays are readily available for measuring insulin, gastrin, vasoactive

intestinal peptide (VIP), and glucagon. Assays for somatostatin, pancreatic polypeptide (PP),

prostaglandins, and other hormonal markers are less commonly available but can be obtained from

certain laboratories. The third step involves localizing and staging the tumor in preparation for possible

operative intervention (Algorithm 56-1).

LOCALIZATION AND STAGING

Computed Tomography

4 The initial imaging technique used to localize a PEN and stage the disease is high-quality

multidetector three-dimensional CT.50 The accuracy of CT in detecting primary PENs ranges from 64%

to 82% and depends largely on the size of the tumor.51,52 PENs are typically hyperdense (bright) on

arterial phases of imaging. Lesions that are obvious during the early arterial phase can become isodense

on later phases of imaging. Therefore, a multiphase approach is typically recommended.53,54 CT is

useful in assessing size and location of the primary tumor, proximity to visceral vessels, peripancreatic

lymph node involvement, and the presence or absence of liver metastases (Fig. 56-1).

Magnetic Resonance Imaging

MRI is increasingly used in the detection of PENs, particularly small lesions. They are especially well

visualized on T1- and T2-weighted images with fat suppression. MRI has the advantage of increased soft

tissue contrast without the administration of intravenous contrast when compared to CT.42 PENs

characteristically have high signal intensity on T2-weighted images.55 On dynamic contrast-enhanced

T1-weighted images, the tumors show the same typical enhancement pattern as on CT scan. The

sensitivity of MRI has been reported to be between 74% and 100%.51,52

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Algorithm 56-1. Diagnosis and management of pancreatic endocrine neoplasms.

Somatostatin Receptor Scintigraphy (Octreoscan)

Somatostatin receptor scintigraphy (SRS) also plays an important role in imaging patients with

pancreatic endocrine tumors.56–62 In this technique, the octapeptide analog of somatostatin (Octreotide)

labeled with indium-111 is administered intravenously to patients in whom a PEN is suspected. Because

neuroendocrine tumors often express large numbers of somatostatin receptors on their cell surfaces (Fig.

56-2), the tracer preferentially identifies tumors. The overall sensitivity of SRS has been reported to

range from 74% to near 100% depending on the functional type of PEN.63 There is a significant falsenegative rate, indicating that negative SRS findings in patients with PENs should be viewed with

caution. Nonfunctional tumors and insulinomas seem to be localized less frequently by SRS, while SRS

performs well for gastrinoma, VIPoma, and glucagonoma. In addition, SRS appears to play a role in the

evaluation of patients with metastatic pancreatic endocrine tumors, especially in identifying

extrahepatic tumor spread. In a study by Frilling et al.,62 54% of patients with liver metastases had

extrahepatic tumor spread detected by SRS that was not detected by alternate imaging techniques.

Figure 56-1. Computed tomography with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The

neoplasm (arrow) is seen as a contrast-enhancing structure, 3 cm in diameter, in the tail of the pancreas posterior to the stomach

(S). (From Yeo CJ. Islet cell tumors of the pancreas. In: Niederhuber JE, ed. Current Therapy in Oncology. St. Louis, MO: Mosby;

1993:272, with permission.)

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Figure 56-2. Octreotide scan (anterior view) in a patient with a large endocrine tumor in the tail of the pancreas (large dark mass,

upper right) and several hepatic metastases (upper left quadrant). A small amount of the tracer is seen in the bladder (lower

midline).

Endoscopic Ultrasound

5 Endoscopic ultrasonography (EUS) has also shown utility in localizing PENs.64–68 Rosch et al.67 were

able to localize 32 of 39 tumors (82%) correctly with EUS after CT had failed to locate the tumor (Fig.

56-3). In their experience, EUS was more sensitive than the combination of CT and visceral

angiography. A more recent study by Proye et al.69 evaluated preoperative EUS and SRS in 41 patients

with insulinoma and gastrinoma. The sensitivity and positive predictive value of EUS were 77% and

94%, respectively, for pancreatic tumors; 40% and 100%, respectively, for duodenal gastrinomas; and

58% and 78%, respectively, for metastatic lymph nodes. These results indicate that EUS is best at

detecting lesions in the head of the pancreas. It is less successful at evaluating the distal pancreas and

the duodenal wall. Additionally, the procedure is operator dependent.70 These results have been

duplicated by others and have led some to suggest that EUS should serve as the initial localization

procedure in patients with insulinoma and gastrinoma. Of note, the drawback to EUS is that it does not

evaluate accurately for hepatic metastatic disease; rather, it is more sensitive than CT for imaging the

duodenal wall, pancreatic parenchyma, and peripancreatic lymph nodes.

Intraoperative Ultrasound

Historically, the primary methods of localizing PENs intraoperatively have been visualization and

palpation. With the advent of laparoscopic exploration for PENs, intraoperative ultrasound has been

substituted for palpation. Results have been promising, with sensitivities reported between 75% and

90%.71,72

Figure 56-3. Endoscopic ultrasonographic image from a patient with an insulinoma (arrows) in the body of the pancreas. SV,

splenic vein. (From Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic

ultrasonography. N Engl J Med 1992;326:1721–1726, with permission.)

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