Preoperative Tumor Localizing Techniques

Tumor-localizing techniques for gastrinoma have continued to evolve since Zollinger and Ellison's first report.1 Their first two Z-E syndrome patients had only barium swallows, demonstrating mucosal changes in the stomach and small bowel related to excess acid. In Ellison's 1956 report, the first reported "series" of ulcerogenic tumor patients, no tumors were identified preoperatively by any imaging technique, and the concept of preoperative localizing was not even mentioned. Abdominal plain films and barium studies




FIGURE 82-2. Serum gastrin concentrations before and after the intravenous injection of secretin (2 U/kg body weight). The test was performed before (circles) and after (triangles) resection of a 5-mm submucosal duodenal wall gastrinoma from a patient with near-normal serum gastrin concentration.

TABLE 82-2. Preoperative Gastrinoma-Localizing



(True Positive %

) References


Abdominal ultrasound


87, 68, 83, 84

Computed tomography


68, 84, 85

Magnetic resonance




Somatostatin receptor


28. 72, 73, 74



Endoscopic ultrasonography



Selective abdominal


28, 68. 71, 86


Transhepatic portal venous


38, 79, 80, 87


Selective arterial secretin


38, 80, 81, 82

injection* with hepatic vein

sampling for gastrin

•Regionalization, not true localization.

are not helpful unless there is a large, bulky tumor or calcification in a pancreatic islet cell tumor. Sensitivities for preoperative gastrinoma-localizing modalities are given in Table 82-2. Practical steps for ordering preoperative localizing studies are listed in Table 82-3.

Abdominal ultrasonography (US) has a low detection rate (20% to 25%) for gastrinomas but is relatively inexpensive and does not involve the risks associated with intravenous contrast material and radiation exposure that accompany computed tomography. Tumors smaller than 1 cm are generally not detected, and only 15% of lesions 1 to 3 cm in size are detected. Tumors larger than 3 cm are usually seen.67 Despite its poor sensitivity, US may improve the overall sensitivity for detecting a tumor if it is used in conjunction with other studies.68

TABLE 82-3. Practical Steps for Ordering Preoperative Localizing Studies

1. Before any localizing studies are done, confirm diagnosis (i.e., gastrin determination and gastric analysis).

2. Perform CT scan and/or MRI of abdomen. These are the most sensitive imaging modalities to show liver metastases. Other localizing studies are not required if liver metastases are documented.

3. Perform EUS, which often identifies small (<1 cm) duodenal wall tumors, paraduodenal lymph nodes, and pancreatic tumors not seen with CT and angiography.

4. Perform selective abdominal angiography combined with SASI test. Gastrinomas are detected in 80% to 100% of Z-E patients when these tests are performed together.

5. Perform somatostatin receptor scintigraphy (optional). This new test is useful for detecting distal metastases and extrapancreatic gastrinomas. False-negative rates are high in some early reports.

CT, computed tomography; EUS, endoscopic ultrasonography; MRI, magnetic resonance imaging; SASI. selective arterial secretin injection; Z-E, Zollinger-Ellison.

Computed tomography (CT) overshadowed abdominal angiography during the 1980s and became a popular gastrinoma-localizing technique. Early reports enthusiastically suggested that CT of the upper abdomen would detect nearly 70% of islet cell tumors found at laparotomy.69 However, even with the new-generation CT scanners and improved techniques, most modern studies indicate that CT identifies a gastrinoma in fewer than half of all Z-E patients.28 CT rarely detects tumors smaller than 1 cm and finds less than 50% of 2-cm lesions. Preoperative CT has been important, however, to identify liver metastases. Two-phase helical CT scans abdominal organs in both the arterial and parenchymal phase after intravenous contrast. In a 1995 report, 9 of 11 islet cell tumors were identified (82% sensitivity), including a 4-mm gastrinoma.70 This new technique could improve detection of gastrinomas.

Magnetic resonance (MR) imaging has not demonstrated great sensitivity for localizing primary gastrinomas. Advantages of MR include the ability to obtain coronal and sagittal images and to identify liver metastases. A 1993 study from the National Institutes of Health (NIH) group that prospectively compared MR with US, CT, and angiography in 32 gastrinoma patients showed sensitivities of only 25%, 19%, 28%, and 59%, respectively.71 However, for the 18 patients in the study with metastatic gastrinoma in the liver, MR imaging had a sensitivity of 83%, whereas the sensitivities of US, CT, and angiography were 50%, 56%, and 61%, respectively. The combination of MR, US, and CT was the same as MR alone. They concluded that MR is the imaging study of choice to assess metastatic pancreatic endocrine tumors in the liver. In contrast, the detection of primary tumors by MR imaging had not improved; therefore, they also recommended that angiography remain the study of choice for localizing primary tumors. MR imaging technology is improving, and, with reduced scanning times, image resolution may equal or exceed that of CT.

Somatostatin receptor scintigraphy (SRS) is a new technique to localize gastrointestinal endocrine tumors. Because many of these tumors possess high-affinity somatostatin receptors, it is possible with the stable indium-lll-labeled somatostatin analogue pentetreotide, which binds to these receptors, to detect somatostatin receptor-positive tumors scintigraphically. Several studies suggest that SRS is helpful in the preoperative localization of gastrointestinal endocrine tumors.72'73 One study detected gastrinomas at a rate of 100% compared with 60% each for CT, MR, and percutaneous abdominal US.74

Endoscopic ultrasonography (EUS) has been shown to image the pancreas accurately and to be highly sensitive for small pancreatic adenocarcinomas.75 The University of Michigan group reported that EUS correctly identified and localized 7 of 10 insulinomas, all in the pancreas, but only 1 of 5 gastrinomas. Three "missed" gastrinomas, 3 to 6 mm, were found at operation in the duodenal wall. They concluded that a negative EUS study in Z-E syndrome patients excluded a pancreatic gastrinoma, indicating a small duodenal or extrapancreatic lesion.76 A subsequent prospective study from Paris showed that EUS alone localized gastrinomas in 41% of 22 Z-E syndrome patients.77 Sensitivity of EUS was 50% for duodenal wall tumors (conventional endoscopy, 40%), 75% for pancreatic tumors (CT scan,

25%), and 62.5% for tumoral lymph nodes (CT scan, 0%). They concluded that EUS should be considered as a first-choice imaging technique for preoperative detection of gastrinomas, and, although small duodenal gastrinomas are still obviously difficult to detect, an accurate exploration of the pancreatic area was provided by this technique. Both the Michigan and Paris groups suggested that laparotomy could be performed in most Z-E syndrome patients after only two imaging studies: CT scan and EUS. Sensitivity of EUS is related not only to tumor size but also to the experience of the endoscopist and radiologist performing EUS. There is a learning curve, and 100 cases may be needed to become proficient.76

Selective abdominal angiography was first used to detect a pancreatic islet cell tumor (an insulinoma) in 1963.78 The sensitivity of angiography in detecting gastrinoma has been considerably less than that for insulinoma, even with the new ancillary techniques that improve sensitivity, such as superselective vessel injection, magnification, and digital subtraction angiography. Selective angiography has proved to be the best imaging study to identify primary and metastatic gastrinoma compared with US, CT, and MRI.28 However, in this study, angiography rarely identified duodenal wall tumor or lymph node metastases.

Portal venous sampling (PVS) is a fluoroscopically guided, percutaneous transhepatic catheterization procedure that obtains venous samples for gastrin from several different veins draining the pancreas or other areas of interest. Gradients in gastrin concentration "regionalize" the tumor location.79 This test requires considerable expertise and has significant complications. PVS has now been replaced by the selective arterial secretin injection (SASI) test because the latter is more sensitive and patients experience fewer complications.80

The SASI test was developed by Imamura and colleagues to localize preoperatively gastrinomas that could not be seen by conventional imaging techniques.81 The principle of the SASI test is based on the observation that secretin injection induces a prompt release of gastrin from gastrinoma cells.65 An arterial catheter is selectively inserted into one of three peripancreatic arteries: gastroduodenal, superior mesenteric, or splenic artery. The gastroduodenal artery feeds the upper half of the pancreatic head and upper duodenum. The splenic artery supplies the body and tail of the pancreas. The superior mesenteric artery feeds the lower half of the pancreatic head and the lower duodenum. A second catheter is placed in the right hepatic vein to collect venous samples for gastrin. Secretin is injected into the selected artery, and the hepatic venous blood samples are collected for gastrin measurement before and then 20, 40, 60, 90, and 120 seconds after each secretin injection. Gastrin concentration in the hepatic vein samples obtained after secretin injection into the selected artery supplying the area of duodenum or pancreas containing the gastrinoma peaks earlier and higher than when injected into an artery feeding an area without gastrinoma (Fig. 82-3). In a report by Imamura and Takahashi, the SASI test localized gastrinomas in 12 of 12 Z-E syndrome patients studied, whereas CT and transhepatic PVS had a positive predictability of less than 10%. Selective arteriography identified tumors in only 5 of 12 patients.82"87


PRE 20 40 60 90 120


FIGURE 82-3. Results of selective arterial secretin injection test in a patient with Zollinger-Ellison syndrome with a gastrinoma in the second portion of duodenum. The chart shows hepatic vein serum gastrin concentrations after arterial secretin injection (25 U) into three different arteries supplying the pancreas and duodenum. A positive gradient occurred 20 seconds after injection into the superior mesenteric artery (SMA). This vessel supplies the blood to the second portion of the duodenum through the inferior pancreaticoduodenal arteries.

PRE 20 40 60 90 120


FIGURE 82-3. Results of selective arterial secretin injection test in a patient with Zollinger-Ellison syndrome with a gastrinoma in the second portion of duodenum. The chart shows hepatic vein serum gastrin concentrations after arterial secretin injection (25 U) into three different arteries supplying the pancreas and duodenum. A positive gradient occurred 20 seconds after injection into the superior mesenteric artery (SMA). This vessel supplies the blood to the second portion of the duodenum through the inferior pancreaticoduodenal arteries.

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