Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 6, 2020; 8(17): 3697-3707
Published online Sep 6, 2020. doi: 10.12998/wjcc.v8.i17.3697
Somatostatin receptor scintigraphy in the follow up of neuroendocrine neoplasms of appendix
Jelena Saponjski, Djuro Macut, Dragana Sobic-Saranovic, Sanja Ognjanovic, Ivana Bozic Antic, Djordje Pavlovic, Vera Artiko
Jelena Saponjski, Center for Nuclear Medicine, Clinical Center of Serbia, Belgrade 11000, Serbia
Djuro Macut, Sanja Ognjanovic, Ivana Bozic Antic, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
Dragana Sobic-Saranovic, Vera Artiko, Center for Nuclear Medicine Clinical Center of Serbia, Faculty of Medicine University of Belgrade, Belgrade 11000, Serbia
Djordje Pavlovic, University Children's Clinic, Belgrade 11000, Serbia
Author contributions: Saponjski J designed and performed research and wrote the paper; Macut Dj, Sobic Saranovic D and Artiko V designed the research and supervised the report; Ognjanovic S, Bozic Antic I and Pavlovic Dj provided clinical advice and contributed to analysis.
Supported by Ministry of Science, Education and Technology Republic of Serbia, No. 175018.
Institutional review board statement: The study was reviewed and approved by the Ethic Committee of the Faculty of Medicine University of Belgrade No. 1550/V-9 from 31.05.2019.
Informed consent statement: Before each investigation individual patient gave written consent that anonymous data and the results of investigation can be used for clinical, educational and scientific purposes (with the agreement of Ethical Committee Clinical Center of Serbia, Faculty of Medicine University of Belgrade No. 668/6 from 19.04.2018).
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Vera Artiko, PhD, Professor, Center for Nuclear Medicine Clinical Center of Serbia, Faculty of Medicine University of Belgrade, Visegradska 26, Belgrade 11000, Serbia. vera.artiko@gmail.com
Received: May 1, 2020
Peer-review started: May 1, 2020
First decision: June 13, 2020
Revised: June 24, 2020
Accepted: August 13, 2020
Article in press: August 13, 2020
Published online: September 6, 2020
Processing time: 125 Days and 22.3 Hours
ARTICLE HIGHLIGHTS
Research background

Neuroendocrine tumors of appendix (ANETs) known as carcinoids, are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract. Over half of the ANET discovered accidentally following appendectomy are the most often at the early stage, implicating high survival rate. Symptoms typical for carcinoid syndrome are detected in approximately 20%–30% of patients with tumors usually with distant metastases. For the diagnosis of the neuroendocrine neoplasms of appendix, besides biochemical analyses, different imaging methods and histopathology analyses with immunohistochemical staining, we could use somatostatin receptor scintigraphy (SRS) or positron emission tomography with computed tomography (PET/CT). Surgery represent the first-line therapeutic option while in patients with advanced disease can be considered long-acting somatostatin analogues, targeted therapies (everolimus) or peptide receptor radionuclide therapy.

Research motivation

Although there are a lot of papers about application of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumors, there are very rare sporadic cases described about ANETs particularly. Considering that these tumors have specific symptoms and are discovered mainly accidentally, the aim of this paper was to draw more attention about appropriate management and particularly follow up of this tumors using radionuclide methods.

Research objectives

The aim of this investigation is to estimate the role of SRS in the follow up of the patients operated for carcinoid of appendix.

Research methods

The total of 35 patients was investigated, 23 females and 12 males, average age (43.7 ± 17.3 years). All patients had histological diagnosis of ANET (34 carcinoids of appendix and one tubular carcinoid). Majority of tumors have been found incidentally during surgery of: Acute appendicitis (n = 15), perforated appendicitis (n = 2), ileus (n = 3), hysterectomy (n = 3), ruptured ovarian cyst (n = 2), caecal volvulus (n = 1), while 9 patients had diagnosis of appendiceal tumor before the surgery. Seventeen patients had tumor grade (G) G1, 12 G2 and 6 G3. The right hemicolectomy was performed in 13, while the rest of the patients had appendectomy only. SRS was done early (2h) and late (24h) after i.v. application of 740 MBq technetium-99m ethylenediamine-N, N'-diacetic acid Hydrazinonicotinyl-Tyr3-Octreotide (technetium-99m-Tektrotyd, Polatom, Poland). SRS was performed for restaging in all the patients after surgery.

Research results

There were 12 true positive (TP), 19 true negative, 3 false positive and 1 false negative SRS result. Sensitivity of the method was 92.31%, specificity was 86.36%, positive predictive value was 80.00%, negative predictive value was 95.00% and accuracy 88.57%. Receiver Operating Characteristics analysis showed that SRS scintigraphy is a good test for detection TP cases (area Under the Curve of 0.850, 95% confidence interval/CI: 0.710-0.990, P < 001). Single-photon emission computed tomography (SPECT) contributed diagnosis in 7 TP findings. In 10 patients Krenning score was 4 and in 2 was 3. In 8 patients SRS significantly changed the management of the patients (in two surgery was repeated, in 4 somatostatin analogues and in two peptide receptor radionuclide therapy). Median progression-free survival in SRS positive patients was 52 months (95%CI: 39.7-117.3) while in SRS negative patients it was 60 months (95%CI: 42.8-77.1), without statistically significant difference between the two groups (P = 0.434).

Research conclusions

Our results point out that SRS with 99mTc-Tektrotyd is useful for follow up of the patients after surgery of ANETs, and that the results influence significantly to the change in tumor node metastasis classification as well as the further management of the patients. SPECT and estimation of Krenning score had important role in diagnosis. SRS is also valuable tool for the choice of therapy (surgery, somatostatin analogues or peptide receptor radionuclide therapy). If PET/CT with 68Ga-labeled peptides cannot be performed, the special emphasize should be given to hybrid SPECT/CT imaging and to the radioguided surgery. In spite of being a reliable, noninvasive technique for detection of locoregional or distant metastases, it cannot be used as an ANET predictive technique. Although there are not many data in the literature dealing particularly with ANETs, considering that these tumors have specific symptoms and are discovered mainly accidentally, in the emergency conditions, the aim of this paper was to draw more attention about due time and appropriate management and particularly follow up of tumors using radionuclide methods.

Research perspectives

The ideal radiopharmaceutical for scintigraphic diagnosis of NETs has not been discovered, there are a lot of them under investigation. Wider application of hybrid systems (SPECT/CT, SPECT/magnetic resonance imaging) as well as new cadmium-zinc-telluride SPECT and SPECT/CT cameras increased and widened application and increased the accuracy of somatostatin receptor scintigraphy. These radiopharmaceuticals can also be used for radio-guided surgery thus increasing sensitivity and specificity of the method. (18 F)-Fluoro-2-deoxy-D-glucose PET/CT is recommended for detecting of low differentiated or heterogeneous neuroendocrine tumors. Recently, positron emitting radiopharmaceuticals are preffered, such as 68Ga labeled peptides or 18F-fluorodopamine. These radiopharmaceuticals as well as PET/CT provide superior resolution, faster investigation, shorter imaging time and visualization in three dimensions. However, because of their price and availability their application is still not wide enough.