Association for Academic Surgery
Limitations of somatostatin scintigraphy in primary small bowel neuroendocrine tumors

An earlier version of this work as presented as an abstract at the Oncology Session of the Academic Surgical Congress in San Diego, CA on February 4, 2014.
https://doi.org/10.1016/j.jss.2014.05.031Get rights and content

Abstract

Background

Somatostatin receptor scintigraphy (SRS; octreoscan) is used in neuroendocrine tumors to locate the primary tumor site and delineate the extent of disease. SRS has decreased sensitivity for small bowel neuroendocrine tumors (SBNETs). The reasons for SRS nonlocalization are not clear. We sought to determine factors that correlate with successful primary tumor localization by SRS in patients with resected SBNETs, and also identify factors that confound interpretation of SRS reports.

Methods

Records of patients with resected SBNETs were reviewed for SRS results, tumor size, multifocality, N, and M status. Somatostatin receptor 2 (SSTR2) expression was analyzed in resected tumors by quantitative polymerase chain reaction. SRS reports were reviewed and categorized as localizing the primary tumor or not. A nuclear medicine physician independently reviewed available images.

Results

Of 37 patients with preoperative SRS, the primary tumor was localized in 37%. Of all the factors tested, only small tumor size correlated significantly with SRS nonlocalization. Overexpression of SSTR2 was not significantly different between tumors that were or were not localized by SRS, regardless of tumor size. There were three instances where the SRS report did not agree with the nuclear medicine physician's interpretation as to whether SRS localized the primary tumor. In each case, uptake in mesenteric nodes was a confounding factor.

Conclusions

SBNETs <2 cm are most likely to be missed by SRS. SSTR2 expression did not correlate with SRS nonlocalization of the primary tumor. Uptake in mesenteric nodes may help indicate an SBNET primary but can also interfere with its visualization within the small bowel.

Introduction

Small bowel neuroendocrine tumors (SBNETs) are characterized by their small size, indolent growth, and propensity to metastasize to the liver. Approximately 15% of patients present with liver metastases where the primary tumor site is unknown. The vast majority of these are ultimately found in the small bowel [1]. Despite advanced presentation, surgery remains the first line of treatment for this disease, as resection of the primary tumor and aggressive debulking of liver metastases are associated with greater overall and progression free survival [2], [3], [4], [5], [6], [7]. Additionally, patients with unknown primary tumors have worse overall survival compared with patients with known primary sites [8]. Therefore, a thorough search for the primary tumor should be undertaken to afford the patient the best outcome.

Identifying SBNETs is difficult to do endoscopically, and therefore the patient's workup usually includes radiographic imaging. Computed tomography (CT) scans are useful for detecting liver lesions, metastatic adenopathy associated with SBNETs, and occasionally, the primary tumors themselves [9]. Somatostatin receptor scintigraphy (SRS) is another useful method to look for neuroendocrine tumors (NETs), as it surveys the whole body for somatostatin receptor (SSTR) positive lesions [10]. Somatostatin receptors are expressed on a variety of normal and neoplastic tissues and are upregulated in >80% of well-differentiated gastrointestinal (GI) NETs [11]. In humans, there are five known-receptor subtypes, designated SSTR types 1–5. SSTR1 and type 2 are the most common subtypes expressed on GI NETs [11], [12], [13].

The most widely used SRS radioligand is 111In-DPTA-octreotide (Octreoscan), which detects primary and metastatic NETs by binding primarily to SSTR2 but also weakly to SSTR5 [12], [13], [14]. Octreoscan has evolved over the years with improvement in its anatomic localization. The most basic SRS provides only a whole body planar image. SRS combined with single-photon emission CT (SPECT) provides axial images like a standard CT, but does not provide the same anatomic detail as a CT. Recently, SRS combined with SPECT and CT has become the standard of care. This SRS modality combines the nuclear medicine image with the CT images and provides the best SRS-based localization of SSTR2-expressing tumors [15]. An even more sensitive somatostatin analogue imaging modality combines positron emission tomography with a 68Ga-labeled somatostatin analogue, but this has very limited availability in the United States, restricting its use as part of the standard workup for NETs [16], [17].

Although the introduction of SRS has led to significant improvement in NET diagnostics [18], it fails to identify the primary NET in many patients. The detection rate for all NETs by SRS is >75%, but it has decreased sensitivity for SBNETs [10]. Patients with SBNETs often have bulky mesenteric adenopathy, which takes up the radioligand and can obscure detection of the primary SBNET. Most analyses of SRS sensitivity do not attempt to separate the primary tumor from mesenteric adenopathy, which may inflate the specificity ascribed to SRS in detecting primary SBNETs. Given the importance of the identification of the primary tumor in SBNETs, we set out to determine whether specific clinicopathologic factors correlate with successful localization of the primary tumor by SRS.

Section snippets

Patient selection

Patients undergoing surgery for SBNETs were consented for enrollment in an institutional review board-approved neuroendocrine tumor registry. Patients with SBNETs who were operated on at the University of Iowa Hospital between 2005 and 2013 and who also had SRS performed preoperatively were included in this study. The clinicopathologic data gathered from each patient's record was: primary tumor size, Tumor Node Metastasis stage, single versus multifocal tumors, the total number of lymph nodes

Clinicopathologic characteristics

Of 80 patients with pathologically confirmed SBNETs operated on at the University of Iowa Hospital and Clinics in the Neuroendocrine Tumor Registry Database, 37 (46.3%) had preoperative SRS. Of these, 24 patients were male and 13 were female. All but one patient had N1 disease at the time of diagnosis, and all but three patients had M1 disease. Twenty-two patients (59.5%) had multifocal primary tumors, as noted in the surgical pathology report or the operative note, and the average number of

Discussion

The purpose of this study was two-fold. First, given the widespread use of SRS and its decreased sensitivity in SBNET patients, we wanted to determine which factors contribute to the modality's success in locating primary SBNETs. Second, to identify factors on SRS reports that may contribute to provider difficulty in interpreting SRS imaging, we compared the SRS reports with an independent nuclear medicine physician's interpretation of the actual SRS images to identify potential sources of

Acknowledgment

Supported by National Institutes of Health 5T32#CA148062-03 (J.E.M. and S.K.S.).

Authors' contributions: J.E.M., S.K.S., and J.R.H. contributed to the conception and design. J.E.M., S.K.S., Y.M., and J.R.H. did the analysis and interpretation. J.E.M., D.W., and T.M.O'.D. did the data collection. J.E.M. did the writing of the article. S.K.S., Y.M., T.M.O'.D., and J.R.H. did the critical revisions of the article.

References (20)

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