Published online Sep 6, 2020. doi: 10.12998/wjcc.v8.i17.3697
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
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.
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.
The aim of this investigation is to estimate the role of SRS in the follow up of the patients operated for carcinoid of appendix.
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.
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).
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.
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.