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Pancreatic neuroendocrine tumors: insulinoma

What radiological tests are helpful before surgery in localizing these tumors?

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Once the diagnosis is unequivocally established biochemically, the next step in patient management is to localize the insulinoma. Virtually all insulinomas are located within the pancreas. Because these tumors are usually small, sometimes only 1/3 of an inch in diameter, locating these tumors may be elusive even using the best modern-day techniques. Which and in what order localization methods are chosen often depends on the equipment and expertise available at any particular institution. A sequential manner is usually elected, proceeding from the least complicated and generally less expensive, to more complex methods that may require more cooperation by the patient and often are more expensive.

Transabdominal Ultrasound. There is wider variability in the success with this technique than any other. As many as 2/3 of patients may have their insulinomas found by this technique, but the radiologist must have considerable experience and expertise (Figure 1). The advantages include no radiation, least invasive (no IVs, blood sampling, etc.), relatively inexpensive, and when successful, the tumor is defined by precise anatomically location. This test may be omitted by some since in some reports it is successful in only about 10% of patients.

Preoperative ultrasound showing the insulinoma (Pancreatic neuroendocrine tumor), portal vein, inferior vena cava  and aorta Figure 1:
A. Preoperative US showing the insulinoma (between the 2 stars, upper left, measuring 14.6 mm which is slightly larger than 1/2 inch) within the head of the pancreas, portal vein (V, carrying blood from the intestine and pancreas to the liver), inferior vena cava (IVC, carrying all of the blood from the lower body back to the heart), and aorta (A, carrying all of the blood away from the heart).
Intraoperative ultrasound showing the insulinoma (Pancreatic neuroendocrine tumor) B. Intraoperative US on same patient as Fig 4A, showing the tumor (upper left, round and black pointed to by black curved arrows), a short distance from the main pancreatic duct (center, pd with arrow to small black circle)

Computed Tomography (CT). With recent advances in CT technology (speed, high resolution, and image-reconstruction software), triple-phase helical CT is usually the initially obtained imaging study (Figure 2). Although requiring modest radiation exposure, an IV, and more expense, precise anatomic localization can be achieved in about 70% or more of these tumors. Additionally, the remainder of the abdominal organs is imaged in the unusual case of malignant insulinoma that may have spread to other sites (see below).

Preoperative CT scan showing the insulinoma (Pancreatic neuroendocrine tumor), portal vein, inferior vena cava  and aorta Figure 2:
A. CT scan showing an insulinoma (white dot pointed to by yellow arrow) in the body of the pancreas (P with arrows pointing to the body and tail of the pancreas). The stomach (S with green lines up and down) has air (black) and fluid (darker gray) with it (stomach wall at end of lower green line).
Intraoperative CT scan showing the insulinoma (Pancreatic neuroendocrine tumor) B. CT scan showing insulinoma (white dot pointed to by yellow arrow) in junction of head and uncinate portions of pancreas. Just to the right of the insulinoma is the portal vein (white with "tail"–vein from the spleen joining it) carrying blood from intestine and pancreas to liver.

Endoscopic Ultrasound. As with any ultrasound method, the success of this technique relies heavily on the expertise and experience of the endoscopist. It involves comfortable sedation for the patient using IV medication, and an endoscope (flexible lighted tube with a camera on the end) is inserted through the mouth, down the esophagus (swallowing tube), and into the stomach and duodenum. The specialized endoscope is equipped with high resolution ultrasound, and because the stomach is directly in front of the pancreas, and the duodenum wraps around the head and body of the pancreas, the ultrasound apparatus is right next to the pancreas. This allows very high resolution, detailed imaging of the pancreas, with a success rate of about 90% (Figure 3). Obviously, this is more "invasive" for the patient, is more expensive, and the images are not as readily interpreted by the surgeon. While it may be the single best imaging method, CT scan is usually obtained first.

Endoscopic ultrasound (EUS) of insulinoma (Pancreatic neuroendocrine tumor)
Figure 3: Endoscopic ultrasound (EUS) with 3 views:
Top left: the endoscope is in the duodenum (top black hole), with the tumor (insulinoma) shown within the head of the pancreas, and the 2 major blood vessels behind the pancreas (SMA, superior mesenteric artery; SMV, superior mesenteric vein). (When the SMV is joined by the vein from the spleen, it is called the portal vein.)
Top right: similar view as Figure 6A.
Bottom image: This patient's insulinoma had not been found at a prior operation. Prior to reoperation, using the EUS, a needle was inserted into the insulinoma and a tiny sample was taken to verify under the microscope that this was the tumor.

Arteriography, Selective Arterial Calcium Stimulation (SACS). Dating back to the 1970s, arteriography with specialized subtraction views was considered the gold standard of localization, but succeeded in only 50% with few exceptions. Today, arteriography with SACS is generally held in reserve until the final effort at localization because it involves the highest degree of radiologist expertise, the most invasive for the patient, and considerably more expensive. Because most insulinomas have an excellent blood supply, they may show up by their "blush" during the injection of contrast into the arteries feeding the pancreas (Figure 4). (This arterial injection phase imaging is also used during CT imaging.) As an extension of this technique, because insulin secretion is stimulated by calcium, each of the 3 principal arteries that feed different regions of the pancreas can be injected with calcium. Blood is sampled from draining veins after the "calcium-stimulation" and marked increases in the measured insulin narrows the location of the insulinoma to the region fed by that particular artery (Figure 5). Therefore, this technique is not as anatomically precise, but can direct the intraoperative surgical exploration to that region of the pancreas.

Arteriogram with special subtraction view of insulinoma (Pancreatic neuroendocrine tumor) Figure 4:
Arteriogram with special "subtraction" view–making the insulinoma looking black (lower left). The catheter can be seen tracking up the middle of the picture before curling into the specific artery feeding the insulinoma.
Selective arterial calcium stimulation test for insulinoma (Pancreatic neuroendocrine tumor) Figure 5:
Selective arterial calcium stimulation test. Two catheters are inserted, 1 into the aorta (red) then selectively threaded into the 3 arteries feeding the pancreas. After calcium injection, blood is sampled through the second catheter positioned in a vein draining the liver. In this case, the tumor is seen in the head of the pancreas, and injection of the artery serving that region would stimulate a much higher level in the sampled blood than the other 2 arteries.



Figure 6: Intraoperative US showing the small insulinoma
Figure 6: Intraoperative US showing the small insulinoma (black arrow head) with the pancreatic duct (pd, arrow) bending over the tumor, touching one side. This would require very careful removal!

Intraoperative Ultrasound (IOUS). Together with the surgeon's ability to feel the insulinomas, IOUS is perhaps the most helpful localization technique of all—the combination exceeding 95% success (Figure 6). In difficult situations if not routinely, the expertise of a radiologist in the OR is necessary. This is not the only test obtained, however, because surgeons and patients alike are far more comfortable knowing the location of the insulinoma prior to proceeding to the OR. IOUS also helps define critical anatomic relationships such as the arteries, veins, common bile duct, and most importantly, the main pancreatic duct (See below under Complications). Decisions regarding the safest and most effect technique for surgical removal of the insulinoma may be directed by the IOUS findings.

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