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1.
Neuroendocrinology ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531329

RESUMO

Peptide-receptor radionuclide therapy (PRRT) is a targeted molecular therapy used to treat neuroendocrine tumours (NET). It has been shown to be effective and well-tolerated in patients with metastatic neuroendocrine tumours in several centres in United States (US), Europe and Australia. Tolerability and efficacy data emerging from Asian centres remain few. Epidemiological evidence suggests that there are differences in neuroendocrine neoplasms between the population groups. We aim to describe the treatment and safety outcomes of PRRT in the Asian population. Methods One hundred and seven (107) patients with metastatic neuroendocrine tumour who had undergone PRRT treatment from January 2012 to March 2019 were included in this retrospective study. The response rates using RECIST1.1 and qualitative analysis were examined. The overall and progression free survival curves were also evaluated. Results The median progression free survival was 49 months. Response assessment after completion of treatment showed that 33(37.9%) of 87 patients had partial or complete response. Subgroup analysis comparing high- and low-grade NET showed that there was a significant difference in the time to progression curves. Comparison of the number of cycles and progression free and overall survival also showed a significant difference. Ten patients (9%) had grade 3 or more haematological toxicities. Four patients (4%) had grade 3/4 hepatobiliary toxicities, although the presence of extensive liver metastases was a confounding factor. None of the patients had grade 3/4 acute kidney injury. Conclusion Our results show that PRRT is safe and effective in the treatment of metastatic neuroendocrine tumour in the Asian population. There was a significant difference in the progression free survival curves between low-grade and high-grade NET, and in the progression free and overall survival comparing the number of cycles received.

2.
BJR Case Rep ; 10(1): uaad011, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352266

RESUMO

The authors present the case of a 59-year-old lady diagnosed with lymphoepithelial carcinoma (LEC) of the left parotid gland. The primary tumour was identified using contrast-enhanced CT, and diagnosis was confirmed via fine needle aspiration cytology and immunohistochemistry. Staging using fluorine-18 fluorodeoxyglucose PET CT revealed regional nodal metastases, while no distant metastasis was evident. Following radical radiotherapy, a favourable locoregional response was observed on MRI, yet the patient's plasma Epstein-Barr virus load continued to rise. Given her primary tumour's somatostatin receptor type 2 (SSTR2) positivity, gallium-68 DOTA-[Tyr3] octreotate PET CT (68Ga-DOTATATE PET CT) was performed, revealing multiple distant metastases with DOTATATE avidity. Despite attempts at palliative chemotherapy and immunotherapy, disease progression led to the decision for the best supportive care. The unique presentation of metastatic LEC on 68Ga-DOTATATE PET CT suggests a potential role for SSTR2-targeted imaging in diagnosis and management.

3.
J Neuroendocrinol ; 35(12): e13349, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37937484

RESUMO

INTRODUCTION: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature. METHODS: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed. RESULTS: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL. CONCLUSION: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/radioterapia , Radioisótopos de Ítrio , Estudos Retrospectivos , Paraganglioma/radioterapia , Neoplasias das Glândulas Suprarrenais/radioterapia , Receptores de Peptídeos
4.
Clin Nucl Med ; 48(12): 1056-1058, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37844551

RESUMO

ABSTRACT: We present a case of a 59-year-old woman with lymphoepithelial carcinoma of left parotid gland. She was treated with radical radiotherapy, but her plasma Epstein-Barr virus DNA load continued to increase despite good locoregional response. As her primary tumor was positive for somatostatin receptor type 2, we performed 68 Ga-DOTATATE PET/CT, which revealed multiple DOTATATE-avid distant metastases.


Assuntos
Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Compostos Organometálicos , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Glândula Parótida , Herpesvirus Humano 4
5.
J Immunother Cancer ; 11(8)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37586766

RESUMO

BACKGROUND: Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown. METHODS: By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial. RESULTS: We found that higher tumor mutation burden, NCOR1 mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9+/CXCR3+ macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy. CONCLUSIONS: This study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Microesferas , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Deleção Cromossômica
6.
Liver Cancer ; 11(5): 451-459, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36158588

RESUMO

Introduction: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC). Methods: A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy. Results: Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13.6 months (95% CI: 5.4-21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3-25.2) and the median PFS was 9 months (95% CI: 3.2-13.1). The response rate was 25% (95% CI: 3.8-46.2%), and the disease control rate was 75% (95% CI: 53.8-96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2). Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.

7.
Cancers (Basel) ; 14(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35892843

RESUMO

Adenoid cystic carcinoma (ACC) and other salivary gland cancers (SGCs) are rare tumors where application of prostate specific membrane antigen (PSMA) positron emission tomography (PET) and PSMA radioligand therapy have yet to be studied extensively. This review explores the role of PSMA PET imaging and therapy as a theranostic tool for ACC and other SGCs based on current literature. A comprehensive literature search on PubMed and Embase was performed. All relevant studies containing information on PSMA PET imaging in ACC and SGC were included. Ten studies (one prospective, three retrospective, five case reports and one review paper) were included. For ACC, the mean maximum standardized uptake value (SUVmax) for local recurrence and distant metastases ranged from 2.41 to 13.8 and 2.04 to 14.9, respectively. In SGC, the meanSUVmax ranged from 1.2-12.50. Most studies observed PSMA expression positivity on immunohistochemistry (IHC) when there was PSMA PET uptake. PSMA PET was able to detect lesions not detected on standard imaging. Despite the small number of studies and wide intra-patient and inter-tumor variation of PSMA uptake in ACC and SGC, 68Gallium (68Ga)-PSMA PET has promising prospects as a diagnostic and radioligand therapeutic option. Further studies to answer the various theranostics considerations are required to guide its use in the real-world setting.

8.
Clin Nucl Med ; 47(6): 547-548, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025804

RESUMO

ABSTRACT: A 61-year-old woman with well-differentiated thyroid cancer underwent 124I-PET/CT imaging. A 124I capsule was administered orally, and the patient was imaged 90 minutes after from the skull vertex to feet. The 124I capsule was unexpectedly lodged in the esophagus. We illustrate attenuation and scatter correction artifacts from 124I capsule unexpectedly lodged in the esophagus and the usefulness of nonattenuation correction images in such circumstances. This also highlights the importance of drinking adequate amounts of water following the ingestion of iodine capsules (123I, 124I, or 131I) to reduce the resulting radiation dose to the esophagus.


Assuntos
Radioisótopos do Iodo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Artefatos , Esôfago/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos
9.
Clin Nucl Med ; 47(4): 321-323, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35020655

RESUMO

ABSTRACT: Anastomosing hemangioma (AH) is a rare benign vascular lesion that primarily involves the genitourinary tract. Cases have also rarely been reported in other organs. AH is often discovered incidentally and resembles angiosarcoma histologically. On imaging, it may mimic other vascular lesions such as renal cell carcinoma and neuroendocrine tumors. We present a case of a 32-year-old woman with incidentally detected AH involving the kidneys, adrenal glands, liver, and retroperitoneum, initially presumed to be neuroendocrine tumors based on imaging findings on CT and 68Ga-DOTATATE PET scans.


Assuntos
Hemangioma , Neoplasias Renais , Tumores Neuroendócrinos , Compostos Organometálicos , Adulto , Feminino , Hemangioma/diagnóstico por imagem , Hemangioma/patologia , Humanos , Neoplasias Renais/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Cintilografia
10.
Lancet Gastroenterol Hepatol ; 6(12): 1025-1035, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34695377

RESUMO

BACKGROUND: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. METHODS: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed. FINDINGS: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). INTERPRETATION: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. FUNDING: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Nivolumabe/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/patologia , Masculino , Microesferas , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Segurança , Índice de Gravidade de Doença , Singapura/epidemiologia , Resultado do Tratamento , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/metabolismo
11.
Front Genet ; 12: 721832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512731

RESUMO

BACKGROUND: The standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19-40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly. METHODS: We identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence. RESULTS: The multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state. CONCLUSION: Using a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.

12.
Liver Cancer ; 10(3): 224-239, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34239809

RESUMO

INTRODUCTION: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). METHOD: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). RESULTS: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. CONCLUSION: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.

13.
Nat Commun ; 12(1): 117, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402692

RESUMO

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.


Assuntos
Infecções por Vírus Epstein-Barr , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Receptores de Somatostatina , Proteínas da Matriz Viral , Animais , Feminino , Humanos , Masculino , Camundongos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Metástase Linfática , Camundongos Nus , Terapia de Alvo Molecular , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/virologia , NF-kappa B/genética , NF-kappa B/metabolismo , Octreotida/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Somatostatina/antagonistas & inibidores , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transdução de Sinais , Análise de Sobrevida , Proteínas da Matriz Viral/antagonistas & inibidores , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Clin Endocrinol Metab ; 106(5): e2299-e2308, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33462615

RESUMO

CONTEXT: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. CASE DESCRIPTION: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. CONCLUSION: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Histiocitoma Fibroso Benigno/metabolismo , Osteomalacia/etiologia , Síndromes Paraneoplásicas/etiologia , Neoplasias de Tecidos Moles/etiologia , Adulto , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Doenças do Pé/diagnóstico , Doenças do Pé/etiologia , Doenças do Pé/genética , Doenças do Pé/metabolismo , Regulação Neoplásica da Expressão Gênica , Histiocitoma Fibroso Benigno/complicações , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/genética , Humanos , Malásia , Masculino , Osteomalacia/diagnóstico , Osteomalacia/genética , Osteomalacia/metabolismo , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/genética , Síndromes Paraneoplásicas/metabolismo , Singapura , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo
15.
Clin Endocrinol (Oxf) ; 94(3): 504-512, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32886805

RESUMO

BACKGROUND: American Thyroid Association (ATA) low-intermediate-risk papillary thyroid cancer (PTC) patients without structural and biochemical evidence of disease on initial post-treatment evaluation have a low risk of recurrence. Studies have shown that with current ultrasound scans (US) and thyroglobulin assays, recurrences mostly occurred 2-8 years after initial therapy. The ATA recommends that neck US be done 6-12 months after surgery to establish patient's response to therapy, then periodically depending on risk of recurrence. The lack of clarity in recommendations on timing of follow-up US and fear of recurrence leads to frequent tests. OBJECTIVES: To evaluate the utility of routine neck US in ATA low-intermediate-risk PTC patients with no structural disease on neck US and non-stimulated thyroglobulin <1.0 ng/mL after initial therapy. METHODS: A retrospective study of 93 patients from Singapore, Saudi Arabia and Argentina with ATA low (n = 49) to intermediate (n = 44) risk PTC was conducted between 1998 and 2017. The outcome was to measure the frequency of identifying structural disease recurrence and non-actionable US abnormalities. RESULTS: Over a median follow-up of 5 years, five of the 93 patients (5.4%) developed structural neck recurrence on US at a median of 2.5 years after initial treatment. Indeterminate US abnormalities were detected in 19 of the 93 patients (20.4%) leading to additional tests, which did not detect significant disease. CONCLUSION: In ATA low-intermediate-risk PTC with no suspicious findings on neck US and a non-stimulated thyroglobulin of <1.0 ng/mL after initial therapy, frequent US is more likely to identify non-actionable abnormalities than clinically significant disease.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
16.
J Radiol Prot ; 41(4)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32434155

RESUMO

With increasing use of recombinant human TSH (rhTSH) stimulation protocol in radioactive iodine-131 treatment of thyroidectomised differentiated thyroid carcinoma (DTC), there is increasing concern regarding radiation safety during collection and processing of radioactive blood samples. Our study aims to quantify this radiation exposure in the context of current radiation guidelines to provide a practical safety framework. We analysed 45 patients prospectively referred to a tertiary centre in Singapore, who had histologically proven DTC, and who were thyroidectomised and planned for I-131 with rhTSH stimulation. Each patient received rhTSH for two consecutive days, with I-131 administered 24 h after, and a stimulated Thyroglobulin blood sample collected and processed 72 h after the last rhTSH dose. We measured radiation exposures with dosimeters. Based on the average and maximum exposure rates calculated, we extrapolated and derived the number of radioactive blood samples that could be safely collected and processed. Mean hand and body radiation exposures during venepuncture and blood processing were generally significantly higher than background radiation. Based on average exposure rates, the permissible number of blood samples that can be collected and processed is 9.09 × 103per year (24 per day) and 8.70 × 104per year (238 per day), respectively. This is the first study to date to extrapolate permissible thresholds that can serve as a practical guideline to the number of radioactive blood samples which can be safely collected and processed, following radioactive iodine therapy, within the limits of current radiation guidelines. Once validated, generalisations to other radioactive therapies may be considered.


Assuntos
Exposição à Radiação , Neoplasias da Glândula Tireoide , Tirotropina Alfa , Pessoal Técnico de Saúde , Humanos , Radioisótopos do Iodo , Proteínas Recombinantes , Tireotropina
18.
J Nucl Med Technol ; 48(2): 98-101, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32358044

RESUMO

The COVID-19 outbreak was declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Since then, the virus has spread to affect more countries worldwide. During this period, our nuclear medicine department at Singapore General Hospital segregated our staff and patients by time, by space, or both, to minimize contact and prevent spread of the virus. Necessary changes to our clinical practices and stricter infection control measures were also enforced. We share our personal experience in managing a nuclear medicine department during this epidemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Departamentos Hospitalares , Controle de Infecções/métodos , Medicina Nuclear , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , COVID-19 , Humanos , Exposição Ocupacional/prevenção & controle , Segurança do Paciente , Singapura
20.
Eur J Nucl Med Mol Imaging ; 47(7): 1645-1648, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32232520

RESUMO

PURPOSE: The aim of this short communication is to outline our experience in policies and processes of a nuclear medicine service during the COVID-19 outbreak in Singapore. METHODS: We describe the key considerations of policies and processes that have been implemented in our nuclear medicine service since the first case of COVID-19 was confirmed in Singapore General Hospital on 23 January 2020, up to the present time. RESULTS: Infection control, screening of patients and visitors, segregation of risk groups, segregation of staff and service continuity plans, communication and staff welfare, using electronic platforms for multi-disciplinary meetings and tele-reporting are discussed. CONCLUSION: Since our hospital received the first patient with COVID-19 in Singapore, our centre has managed 16 COVID-19 cases to date. There has not been any healthcare worker in our institution who has contracted COVID-19 through patient contact. We have highlighted for discussion some of the policies and processes to prepare a nuclear medicine service for the COVID-19 threat.


Assuntos
Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Medicina Nuclear , Pneumonia Viral/epidemiologia , COVID-19 , Comunicação , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Relatório de Pesquisa , Risco , Segurança
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