Imaging and localization of pancreatic insulinomas
Introduction
Insulinomas are the most frequent functioning islet cell tumors [1]. There is a 2:1 female predominance, occurring in the fifth and sixth decades of life. About 10% are multiple, 10% are malignant and 4% are associated with multiple endocrine neoplasia type 1 [2], [3]. The clinical presentation is the Whipple triad (symptoms of hypoglycaemia, low blood glucose levels and symptomatic relief with glucose administration).
The tumors are often small; 90% are <2 cm in diameter. Preoperative localization is very important with significant reduction of the operative time. Despite the availability of all state-of-the-art imaging techniques, the localization of these tumors remains a challenge for the radiologist. Ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), arteriography, intraarterial stimulation with venous sampling (ASVS), somatostatin receptor scintigraphy (SRS) and endoscopic (EUS) and intraoperative US (IOUS) are all available for the investigation of insulinomas, with variable success.
The purpose of this paper is to demonstrate the imaging characteristics, the sensitivity and the role of all the variable techniques in the diagnostic algorithm of these unique tumors.
Section snippets
Ultrasound
The sensitivity of US ranged from 9% to 63% [4], [5], [6], [7], [8], [9] in most published series and the main problems for this low visualization rate are the small tumor size, the overlying bowel gas and obesity. Visualization of tumors located in the pancreatic tail is more difficult due to overlying bowel gas. Patients with hyperinsulinism are often obese, because they eat excessive amounts of food in order to alleviate symptoms. Recently, Angeli et al. [10] reported a sensitivity of 79.3%
Computed tomography
The sensitivity of conventional CT is disappointingly low, with a range of 16–72% [4], [5], [6], [7], [8], [9], [10], [11]. Helical CT improved the detection rate of insulinomas [12], [13], [14]. Van Hoe et al. [12] detected five of six insulinomas (four on the arterial and one on the parenchymal phase images). The insulinoma, which was not detected, was 4 mm in size. Chung et al. [13] demonstrated four of five insulinomas in the arterial phase. After the reconstruction of 2-D multiplanar
Magnetic resonance imaging
The sensitivity of MRI is as high as 65.5% [5], [7], [8], [9], [10], [11]. Moore et al. [20] demonstrated three out of four insulinomas. Their typical appearance is of low-signal intensity on T1-weighted SE images and high-signal intensity on T2-weighted SE images. The short inversion time recovery (STIR) sequence and fat-suppressed fast spin-echo T2-weighted images are the most useful techniques [11], [20], [21], [22], [23], [24]. The tumor is bright on STIR sequences and has reduced signal
Angiography
Angiography has successfully localized insulinomas in 36–91% of cases [4], [5], [6], [7], [8], [9], [10], [11]. Selective catheterization of the celiac trunk, hepatic, splenic and superior mesenteric arteries is performed. If possible, superselective injections into the gastroduodenal, dorsal pancreatic superior and inferior pancreaticoduodenal arteries may provide additional information. The presence of focal, well-circumscribed, hypervascular mass normally in the arterial phase is diagnostic
Intraarterial calcium stimulation with venous sampling
ASVS is performed simultaneously with angiography. A second catheter is advanced into the right hepatic vein. A dose of 0.025 mEq/kg calcium gluconate is injected into the superior mesenteric, proximal and distal (beyond the origin pancreatic magna artery) splenic and gastroduodenal arteries. Blood samples are obtained from the right hepatic vein at 0, 30, 60, 90 and 180 s after calcium infusion. Insulin levels are measured by radioimmunoassay. A positive provocative study result is defined by
Endoscopic ultrasonography
EUS has a sensitivity as high as 93% for the detection of insulinomas [27], [28], [29], [30], [31], [32]. The sensitivity depends on the location and volume of the tumor. Schumacher et al. [29] had sensitivity 83% for tumors located at the head and 37% at the tail of pancreas. This is due to the fact that visualization rate of EUS is low in the pancreatic tail. The lesion size is usually underestimated with EUS, because of the 2-D nature of measurements. Extensive exploration of the entire
Somatostatin receptor scintigraphy
SRS is performed with indium 111-pentetreotide. Planar images are acquired with a γ-camera. Patients undergo anterior and posterior whole body static scintigraphy. Planar images are obtained 4 and 24 h after administration of the tracer, followed by SPECT images of the region of interest [31], [32].
SRS has a sensitivity as high as 60% [33]. Selective octreotide uptake is mainly due to the presence of type 2 somatostatin receptors in insulinomas (Fig. 8)[34]. Factors affecting the sensitivity
Intraoperative US
IOUS is the most sensitive method for localization of insulinomas, with an accuracy of 86–100% [8], [35]. It is more sensitive than palpation [4], [36]. IUS can not only detect a small tumor but can also demonstrate its relationship to the pancreatic and common bile duct and adjacent blood vessels. Special attention is necessary to avoid injury of the pancreatic duct during IOUS. The ultrasonographic appearance of insulinoma is typically hypoechoic.
Algorithm of management
The treatment of choice for insulinomas is resection. At least two clear positive localizations with noninvasive modalities are favourable. Failure to obtain this goal does not contraindicate surgical exploration. If there is a referral center with experienced surgeons and radiologists for IOUS, patients should be directed to it and preoperative localization with invasive methods is not absolutely required [37]. If insulinoma is not detected during operation, ASVS technique is performed
Conclusion
The localization of insulinomas is a challenge to the radiologist and requires meticulous attention to detail in technique. The choice of the imaging studies for the localization of these tumors depends on the existence of a referral center with experienced surgeons and radiologists [36]. The most sensitive preoperative technique is ASVS, whereas IOUS is the most accurate intraoperative method.
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