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Pediatric Ectopic Cushing Syndrome Caused by Hepatic Neoplasms: A Case Report and Systematic Review.Cureus Mar 2023Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an...
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an adolescent boy who presented with Cushingoid features and had endogenous ACTH-dependent hypercortisolism on hormonal evaluation. Abdominal ultrasound and CT revealed a hepatic lesion with characteristics suggestive of hemangioma, whereas the lesion was tracer non-avid on Ga-DOTANOC positron emission tomography/CT. A regional sampling of ACTH was done to confirm the hepatic lesion as the source of EAS, and a definitive ACTH gradient was observed between the hepatic vein and the right internal jugular vein. Further, a preoperative biopsy of the lesion revealed a small round cell tumor with positive immunostaining for ACTH and synaptophysin, suggestive of a neuroendocrine tumor. The patient was managed with partial hepatectomy, resulting in hormonal and clinical remission of Cushing syndrome. In a systematic review of pediatric EAS due to primary hepatic tumors (n = 11), calcifying nested stromal epithelial cell tumors were the most common. EAS-associated hepatic tumors were larger (≥10 cm) except benign primary hepatic neuroendocrine tumors (PHNET). The latter were misdiagnosed as hemangioma in two cases by anatomical imaging but correctly diagnosed by somatostatin receptor scintigraphy. Hepatic tumors causing EAS in children required extensive resection, except benign PHNET. Nevertheless, all benign tumors with an uncomplicated perioperative course demonstrated disease-free survival over a median follow-up period of two years.
PubMed: 37123777
DOI: 10.7759/cureus.36852 -
International Journal of Molecular... Mar 2023Meningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's...
Meningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's surgical and radiation-based treatment are not without complications. No drugs specific for meningiomas are hitherto approved and patients with inoperable or recurrent meningioma are left with few treatment options. Somatostatin receptors are previously detected in meningiomas and may inhibit growth when stimulated by somatostatin. Hence, somatostatin analogs could provide a targeted drug therapy. The aim of this study was to compile the current insights of somatostatin analogs for patients with meningioma. This paper adheres to the PRISMA extension for Scoping Reviews. A systematic search was conducted in the search databases PubMed, Embase via Ovid, and Web of Science. Seventeen papers adhered to the inclusion and exclusion criteria, and critical appraisal was conducted. The overall quality of evidence is low, as none of the studies were randomized or controlled. Various efficacy of somatostatin analogs is reported, and adverse effects are sparse. Due to the beneficial effects reported by some studies, somatostatin analogs may offer a novel last-option treatment for severely ill-patients. Nonetheless, only a controlled study, preferably a randomized clinical trial, could clarify the efficacy of somatostatin analogs.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Octreotide; Randomized Controlled Trials as Topic; Receptors, Somatostatin; Somatostatin
PubMed: 36902224
DOI: 10.3390/ijms24054793 -
Current Medical Imaging 2023Breast cancer is the most common malignancy in women, with high morbidity and mortality. Molecular alterations in breast cancer involve the expression or upregulation of...
BACKGROUND
Breast cancer is the most common malignancy in women, with high morbidity and mortality. Molecular alterations in breast cancer involve the expression or upregulation of various molecular targets that can be used for diagnostic nuclear medicine imaging and radiopharmaceutical treatment. Theragnostics is based on the binding of radionuclides to molecular targets. These radionuclides can induce a cytotoxic effect on the specific tumor cell (target) or its vicinity, thus allowing a personalized approach to patients with effective treatment and comparably small side effects.
AIM
This review aims to describe the most promising molecular targets currently under investigation for theragnostics and precision oncology in breast cancer.
METHODS
A comprehensive literature search of studies on theragnostics in breast cancer was performed in the PubMed, PMC, Scopus, Google Scholar, Embase, Web of Science, and Cochrane library databases, between 2010 and 2022, using the following terms: breast neoplasm*, breast, breast cancer*, theragnostic*, theranostic*, radioligand therap*, RLT, MET, FLT, FMISO, FES, estradiol, trastuzumab, PD-L1, PSMA, FAPI, FACBC, fluciclovine, FAZA, GRPR, DOTATOC, DOTATATE, CXC4, endoglin, gastrin, mucin1, and syndecan1.
RESULTS
Fifty-three studies were included in the systematic review and summarized in six clinical sections: 1) human epidermal growth factor receptor 2 (HER2); 2) somatostatin receptors (SSTRS); 3) prostate-specific membrane antigen radiotracers (PSMA); 4) fibroblast activation protein-α targeted radiotracers; 5) gastrin-releasing peptide receptor-targeted radiotracers; 6) other radiotracers for theragnostics.
CONCLUSION
The theragnostic approach will progressively allow better patient selection, and improve the prediction of response and toxicity, avoiding unnecessary and costly treatment.
Topics: Male; Humans; Female; Breast Neoplasms; Precision Medicine; Radioisotopes; Radiopharmaceuticals
PubMed: 36797602
DOI: 10.2174/1573405619666230216114748 -
Cancers Feb 2023Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature.... (Review)
Review
Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature. Several studies have discussed the expression of progesterone, estrogen, androgen, and somatostatin receptors. The utility of analyzing these expressions for prognostic, theragnostic, and therapeutic purposes remains unclear. The aim of this study was to report the expression of these receptors, based on immunohistochemistry. Cochrane Collaboration guidelines and PRISMA statements were followed. We did an online search in PubMed using the MeSH database. References were selected if the investigations occurred from 1990 to 2022. 61 references were included (34 descriptive observational studies, 26 analytical observational studies, and one case report). In this review, we describe the expression of these receptors in function of age, sex, hormonal context, localization, histological subtype, grade, and recurrence.
PubMed: 36765937
DOI: 10.3390/cancers15030980 -
Seminars in Oncology Dec 2022The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a... (Review)
Review
Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review.
The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was >2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.
Topics: Humans; Female; Middle Aged; Male; Carcinoma, Renal Cell; Kidney Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Pancreas; von Hippel-Lindau Disease
PubMed: 36759234
DOI: 10.1053/j.seminoncol.2023.01.007 -
Pituitary Feb 2023This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared...
PURPOSE
This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness.
METHODS
MEDLINE/Embase/the Cochrane Library (2001-June 2021) and key congresses (2018-2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required.
RESULTS
In total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens.
CONCLUSIONS
Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control.
Topics: Adult; Humans; Acromegaly; Octreotide; Insulin-Like Growth Factor I; Cabergoline; Cross-Sectional Studies; Quality of Life; Peptides, Cyclic; Human Growth Hormone
PubMed: 36447058
DOI: 10.1007/s11102-022-01285-1 -
Current Issues in Molecular Biology Nov 2022We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of... (Review)
Review
We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: Ga-DOTATOC; Ga-DOTATATE; Ga-DOTANOC; Tc-EDDA/HYNIC-TOC; Cu-DOTATATE; and In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: "Somatostatin receptor imaging,"; "Somatostatin receptor imaging" and "Functional,"; "Somatostatin receptor imaging" and "SPECT,"; and "Somatostatin receptor imaging" and "PET". Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between In-DTPA-Octreotide and Ga-DOTATOC/TATE. Few papers compared Cu-DOTATATE and Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for In-DTPA-Octreotide, Tc-EDDA/HYNIC-TOC, Ga-DOTATATE/TOC and Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents.
PubMed: 36354685
DOI: 10.3390/cimb44110373 -
Cancer Imaging : the Official... Sep 2022We aimed to evaluate the prevalence of incidental Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT (SSTR PET/CT) findings, their clinical significance... (Review)
Review
AIM
We aimed to evaluate the prevalence of incidental Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT (SSTR PET/CT) findings, their clinical significance in the need for follow-up, and their risk of malignancy.
MATERIALS AND METHODS
Studies reporting incidental SSTR PET/CT findings were systematically searched in PubMed, Cochrane, Embase and Web of Science literature published prior to 1 of May 2020. Studies were filtered by two independent readers for eligibility based on title and abstract, and subsequently on full text. The main exclusion criteria were: 1) pathological findings that matched scan indication, 2) known organ specific disease and/or incidental findings confirmed on other scan modality prior to SSTR PET/CT, 3) lack of diagnosis and/or follow up, and 4) results published in proceedings or conference abstracts.
RESULTS
Twenty-one studies, comprising a total of 2906 subjects, were eligible for the analysis. Studies included were retrospective cohort studies on incidental SSTR PET/CT findings in a specific organ (n = 2888, 7/21) or case reports (n = 18, 14/21). A total of 133 subjects had incidental SSTR PET/CT findings. Incidental findings were predominantly seen in the thyroid gland (n = 65), spine (n = 30), brain (n = 26) and breast (n = 6). Seventeen of 133 (13%) incidental findings were malignant on final diagnosis. Incidental breast findings were associated with the highest risk of malignancy (67%). In the thyroid, incidental SSTR uptake was caused by malignancy in 8%, all presenting as focal uptake. The lowest risk was seen in the spine with a malignancy rate of 3% in patients with incidental SSTR uptake and benign cases were interpreted as vertebral hemangiomas on CT. Incidental SSTR PET/CT findings in other locations were of malignant etiology in two out of six cases (33%) and should be evaluated individually.
CONCLUSION
The most incidental SSTR PET/CT findings were found in the thyroid gland, spine, and brain. The risk of malignancy was greatest in incidental SSTR PET/CT findings in the breast, cranially, and thyroid gland. The results of the present study can prove useful in the interpretation of atypical findings on SSTR PET/CT and in the counseling of clinicians.
Topics: Heterocyclic Compounds, 1-Ring; Humans; Incidental Findings; Neoplasms; Peptides; Positron Emission Tomography Computed Tomography; Prevalence; Receptors, Somatostatin; Retrospective Studies
PubMed: 36057635
DOI: 10.1186/s40644-022-00484-0 -
Neurosurgical Review Oct 2022Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus... (Meta-Analysis)
Meta-Analysis Review
Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked "very low." Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.
Topics: Everolimus; Humans; Meningeal Neoplasms; Meningioma; Prospective Studies; Receptors, Somatostatin; Somatostatin
PubMed: 35984552
DOI: 10.1007/s10143-022-01849-6 -
Pharmaceutics Jul 2022Somatostatin receptors (SSTR) are expressed in various neoplasms and can be targeted for both diagnostics as well as therapeutics. This systematic review aims to compile... (Review)
Review
Somatostatin receptors (SSTR) are expressed in various neoplasms and can be targeted for both diagnostics as well as therapeutics. This systematic review aims to compile and discuss the prevalence of somatostatin receptor expression in various neoplasms. We performed a literature search from Google Scholar and PubMed using relevant keywords to look for all publicly available data regarding SSTR expression in various cancers. Both histopathological and radiographical studies were included for SSTR assessment. We found that many cancers express SSTR with varying prevalence. SSTR is now a well-established theranostics biomarker. We now have highly sensitive and specific diagnostic modalities like gallium 68 DOTATATE and copper 64 DOTATATE scans to screen for SSTR-2 and then target it therapeutically with lutetium 177 DOTATATE. A thorough understanding of SSTR expression in other tumors will open the channels for exploring potential SSTR targeting.
PubMed: 35890290
DOI: 10.3390/pharmaceutics14071394