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1.
Isr Med Assoc J ; 23(8): 501-505, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392626

RESUMO

BACKGROUND: Multiple myeloma (MM) affects the long bones in 25% of patients. The advent of positron-emission tomography/computed tomography (PET/CT) scanners offers the possibility of both metabolic and radiographic information and may help determine fracture risk. To the best of our knowledge, no published study correlates these two factors with long bone fractures. OBJECTIVES: To evaluate the impact of PET/CT on fracture risk assessment in multiple myeloma patients. METHODS: We identified all bone marrow biopsy proven multiple myeloma patients from 1 January 2010 to 31 January 2015 at a single institution. We prospectively followed patients with long bone lesions using PET/CT scan images. RESULTS: We identified 119 patients (59 males/60 females) with 256 long bone lesions. Mean age at diagnosis was 58 years. The majority of lesions were in the femur (n=150, 59%) and humerus (n=84, 33%); 13 lesions in 10 patients (8%) required surgery for impending (n=4) or actual fracture (n=9). Higher median SUVmax was measured for those with cortical involvement (8.05, range 0-50.8) vs. no involvement (5.0, range 2.1-18.1). SUVmax was found to be a predictor of cortical involvement (odds ratio = 1.17, P = 0.026). No significant correlation was found between SUVmax and pain or fracture (P = 0.43). CONCLUSIONS: Improved medical treatment resulted improvement in 8% of patients with an actual or impending fracture. The orthopedic surgeons commonly use the Mirels classification for long bone fracture prediction. Adding PET/CT imaging to study in myeloma long bone lesions did not predict fracture risk directly but suggested it indirectly by cortical erosion.


Assuntos
Fraturas do Fêmur , Fraturas do Úmero , Mieloma Múltiplo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medição de Risco/métodos , Biópsia/métodos , Medula Óssea/patologia , Osso Cortical/diagnóstico por imagem , Osso Cortical/patologia , Feminino , Fraturas do Fêmur/diagnóstico , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/cirurgia , Fluordesoxiglucose F18/farmacologia , Fixação de Fratura/métodos , Fixação de Fratura/estatística & dados numéricos , Humanos , Fraturas do Úmero/diagnóstico , Fraturas do Úmero/etiologia , Fraturas do Úmero/cirurgia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/patologia , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/farmacologia , Estudos Retrospectivos
2.
Theranostics ; 11(16): 7735-7754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335961

RESUMO

Rationale: Multiple myeloma (MM) is a multifocal malignancy of bone marrow plasma cells, characterized by vicious cycles of remission and relapse that eventually culminate in death. The disease remains mostly incurable largely due to the complex interactions between the bone microenvironment (BME) and MM cells (MMC). In the "vicious cycle" of bone disease, abnormal activation of osteoclasts (OCs) by MMC causes severe osteolysis, promotes immune evasion, and stimulates the growth of MMC. Disrupting these cancer-stroma interactions would enhance treatment response. Methods: To disrupt this cycle, we orthogonally targeted nanomicelles (NM) loaded with non-therapeutic doses of a photosensitizer, titanocene (TC), to VLA-4 (α4ß1, CD49d/CD29) expressing MMC (MM1.S) and αvß3 (CD51/CD61) expressing OC. Concurrently, a non-lethal dose of a radiopharmaceutical, 18F-fluorodeoxyglucose ([18F]FDG) administered systemically interacted with TC (radionuclide stimulated therapy, RaST) to generate cytotoxic reactive oxygen species (ROS). The in vitro and in vivo effects of RaST were characterized in MM1.S cell line, as well as in xenograft and isograft MM animal models. Results: Our data revealed that RaST induced non-enzymatic hydroperoxidation of cellular lipids culminating in mitochondrial dysfunction, DNA fragmentation, and caspase-dependent apoptosis of MMC using VLA-4 avid TC-NMs. RaST upregulated the expression of BAX, Bcl-2, and p53, highlighting the induction of apoptosis via the BAK-independent pathway. The enhancement of multicopper oxidase enzyme F5 expression, which inhibits lipid hydroperoxidation and Fenton reaction, was not sufficient to overcome RaST-induced increase in the accumulation of irreversible function-perturbing α,ß-aldehydes that exerted significant and long-lasting damage to both DNA and proteins. In vivo, either VLA-4-TC-NM or αvß3-TC-NMs RaST induced a significant therapeutic effect on immunocompromised but not immunocompetent MM-bearing mouse models. Combined treatment with both VLA-4-TC-NM and αvß3-TC-NMs synergistically inhibited osteolysis, reduced tumor burden, and prevented rapid relapse in both in vivo models of MM. Conclusions: By targeting MM and bone cells simultaneously, combination RaST suppressed MM disease progression through a multi-prong action on the vicious cycle of bone cancer. Instead of using the standard multidrug approach, our work reveals a unique photophysical treatment paradigm that uses nontoxic doses of a single light-sensitive drug directed orthogonally to cancer and bone cells, followed by radionuclide-stimulated generation of ROS to inhibit tumor progression and minimize osteolysis in both immunocompetent murine and immunocompromised human MM models.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Compostos Organometálicos/farmacologia , Osteoclastos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Medula Óssea/metabolismo , Neoplasias Ósseas , Osso e Ossos/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fluordesoxiglucose F18/farmacologia , Humanos , Cadeias alfa de Integrinas/efeitos dos fármacos , Cadeias alfa de Integrinas/metabolismo , Camundongos , Mieloma Múltiplo/metabolismo , Compostos Organometálicos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteólise/patologia , Radioisótopos/farmacologia , Compostos Radiofarmacêuticos/uso terapêutico , Espécies Reativas de Oxigênio , Transdução de Sinais/efeitos dos fármacos , Nanomedicina Teranóstica/métodos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Circ Cardiovasc Imaging ; 14(3): e011898, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33724049

RESUMO

BACKGROUND: The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS. METHODS: C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day -1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils. RESULTS: Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient (r) of r=0.73 and r=0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET. CONCLUSIONS: Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.


Assuntos
Cicatriz/diagnóstico , Fluordesoxiglucose F18/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Veias/diagnóstico por imagem , Trombose Venosa/diagnóstico , Animais , Cicatriz/etiologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Radiofarmacêuticos/farmacologia , Trombose Venosa/etiologia
4.
PLoS One ; 16(3): e0248193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33667282

RESUMO

OBJECTIVE: We investigated the potential of [18F]fluorodeoxyglucose ([18F]FDG) and [18F]Fluoromethylcholine ([18F]FCho) PET, compared to contrast-enhanced MRI, for the early detection of treatment response in F98 glioblastoma (GB) rats. METHODS: When GB was confirmed on T2- and contrast-enhanced T1-weighted MRI, animals were randomized into a treatment group (n = 5) receiving MRI-guided 3D conformal arc micro-irradiation (20 Gy) with concomitant temozolomide, and a sham group (n = 5). Effect of treatment was evaluated by MRI and [18F]FDG PET on day 2, 5, 9 and 12 post-treatment and [18F]FCho PET on day 1, 6, 8 and 13 post-treatment. The metabolic tumor volume (MTV) was calculated using a semi-automatic thresholding method and the average tracer uptake within the MTV was converted to a standard uptake value (SUV). RESULTS: To detect treatment response, we found that for [18F]FDG PET (SUVmean x MTV) is superior to MTV only. Using (SUVmean x MTV), [18F]FDG PET detects treatment effect starting as soon as day 5 post-therapy, comparable to contrast-enhanced MRI. Importantly, [18F]FDG PET at delayed time intervals (240 min p.i.) was able to detect the treatment effect earlier, starting at day 2 post-irradiation. No significant differences were found at any time point for both the MTV and (SUVmean x MTV) of [18F]FCho PET. CONCLUSIONS: Both MRI and particularly delayed [18F]FDG PET were able to detect early treatment responses in GB rats, whereas, in this study this was not possible using [18F]FCho PET. Further comparative studies should corroborate these results and should also include (different) amino acid PET tracers.


Assuntos
Colina/análogos & derivados , Meios de Contraste/farmacologia , Fluordesoxiglucose F18/farmacologia , Glioblastoma , Imageamento por Ressonância Magnética , Neoplasias Experimentais , Tomografia por Emissão de Pósitrons , Animais , Linhagem Celular Tumoral , Colina/farmacologia , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/terapia , Ratos , Ratos Endogâmicos F344
5.
Medicine (Baltimore) ; 100(12): e25259, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761723

RESUMO

RATIONALE: Although single organ vasculitis (SOV) is a rare occurrence and it is difficult to diagnose, its possibility as a cause of fever of unknown origin (FUO) must be considered. Recently, the usefulness of 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT) in the diagnosis of unknown fevers due to vasculitis, especially in cases of small and medium-sized vasculitis, has begun to be pointed out. PATIENT CONCERNS: We report the case of an 84-year-old woman with persisting fever for more than 2 weeks. She had no accompanying symptoms, other than fever, and the physical examination, echocardiography, and contrast-enhanced CT did not reveal any diagnostic clue. DIAGNOSES: The FDG PET/CT revealed positive uptakes of FDG in the left breast, with a standardized uptake value (SUV) of 2.9. The biopsy specimen of the left breast lesion revealed rupture of the elastic plate and evidence of fibrinoid necrosis of arteries, leading to the diagnosis of polyarteritis (PAN). Further angiographic examination and additional imaging did not reveal the presence of other lesions. Therefore, the diagnosis was established as a PAN-SOV of the left breast. INTERVENTIONS: This patient has improved with follow-up only. OUTCOMES: There has been no evidence of a relapse of PAN over a 5-year follow-up period. LESSONS: SOV presenting with unspecific local symptoms is difficult to diagnose based on the medical history and clinical examination. Our findings show that early "Combination of PET-CT and biopsy" can be a powerful diagnostic tool in patients with FUO for whom diagnosis of the underlying cause is difficult despite appropriate clinical examination.


Assuntos
Biópsia/métodos , Mama , Artéria Torácica Interna , Poliarterite Nodosa , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso de 80 Anos ou mais , Mama/irrigação sanguínea , Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Febre/diagnóstico , Febre/etiologia , Fluordesoxiglucose F18/farmacologia , Humanos , Artéria Torácica Interna/diagnóstico por imagem , Artéria Torácica Interna/patologia , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/fisiopatologia , Compostos Radiofarmacêuticos/farmacologia
6.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33536339

RESUMO

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Modelos Teóricos , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/genética , Feminino , Fluordesoxiglucose F18/farmacologia , Heterogeneidade Genética/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prognóstico
7.
Vet Radiol Ultrasound ; 62(3): 350-359, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33629412

RESUMO

Fluorine-18-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) has been utilized in veterinary medicine to improve the detection and characterization of primary, recurrent, and secondary neoplasms; but its use as a staging tool for dogs diagnosed with appendicular osteosarcoma has not been published. The purpose of this retrospective, case series, descriptive study was to detail the use of 18 F-FDG PET/CT for staging a population of dogs with appendicular osteosarcoma, report the detection rate of secondary neoplastic lesions, and compare findings with published detection rates for other historically used imaging modalities. Seventy-one client-owned dogs with a confirmed diagnosis of appendicular osteosarcoma and staged with a whole-body 18 F-FDG PET/CT scan near the time of initial diagnosis were included. Each PET/CT study was re-evaluated for malignancy distinct from the primary disease entity based on a collective qualitative and quantitative assessment of 18 F-FDG uptake, CT appearance, and contrast enhancement characteristics. Following re-evaluation of each study, information pertaining to tissue sampling performed on identified lesions was retrieved from the medical record when available. Staging with 18 F-FDG PET/CT identified 17 of 71 (23.9%) and 12 of 71 (16.3%) dogs with a high suspicion or confirmation of a metastatic or comorbid malignant neoplasm respectively, with eight of 71 (11.3%) having both metastatic and comorbid lesions. The results of this study are suggestive that 18 F-FDG PET/CT is effective in identifying both osseous and soft tissue secondary neoplastic lesions in dogs afflicted with appendicular osteosarcoma, yielding an increased detection rate of all lesions compared those previously reported for skeletal scintigraphy or whole-body CT.


Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico por imagem , Fluordesoxiglucose F18/farmacologia , Osteossarcoma/veterinária , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/veterinária , Animais , Neoplasias Ósseas/diagnóstico por imagem , Doenças do Cão/patologia , Cães , Humanos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Cintilografia , Compostos Radiofarmacêuticos/farmacologia , Estudos Retrospectivos , Sarcoma/veterinária
8.
Sci Rep ; 11(1): 2475, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510222

RESUMO

Positron (ß+) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a ß+ emitter fluorine-18 (18F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of ß+ emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of ß+ emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for ß+ emitters. These results may also have implications for emerging cancer theranostic strategies, where ß+ emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.


Assuntos
Partículas beta , Elétrons , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata , Linhagem Celular Tumoral , Fluordesoxiglucose F18/farmacologia , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Doses de Radiação , Compostos Radiofarmacêuticos/farmacologia
9.
Support Care Cancer ; 29(8): 4277-4284, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33415364

RESUMO

PURPOSE: Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation. METHODS: We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system. RESULTS: Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8-19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2-41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT. CONCLUSION: Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.


Assuntos
Fluordesoxiglucose F18/efeitos adversos , Inflamação/etiologia , Neoplasias/complicações , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Idoso , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fatores de Risco
10.
BJU Int ; 127(2): 254-262, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33448605

RESUMO

OBJECTIVES: To evaluate diagnostic accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) compared to contrast-enhanced CT in assessment of inguinal lymph node (ILN) metastases, distant metastases and synchronous cancers in patients with penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS: During a 4-year period, patients with pSCC were scheduled for FDG PET/CT prior to surgical treatment at two referral centres that manage all penile cancers in Denmark. The primary endpoint was diagnostic accuracy of FDG PET/CT and of CT alone with histopathology or Response Evaluation Criteria In Solid Tumors (RECIST) as reference. RESULTS: We evaluated 171 patients for distant metastases and synchronous incident cancers and examined 286 groins in 143 patients for LN metastases by FDG PET/CT. Six groins disclosed false negatives. FDG PET/CT sensitivity was 85.4% per patient. In 135 patients (270 groins), CT images were evaluated separately and 22 groins disclosed false negatives. CT sensitivity was 47.5% per patient. FDG PET/CT detected pSCC distant metastases in seven patients. Distant metastases from other cancers were newly detected in three patients. In eight patients, an incidental synchronous cancer was detected. Seven out of the 18 distant malignancies detected depended on FDG PET information. CONCLUSION: This study underlines the increased diagnostic accuracy of FDG PET/CT compared to CT alone in the evaluation of ILN status. In patients with palpable LNs, the advantage of FDG PET/CT over CT is less pronounced. FDG PET/CT may play a role in penile cancer evaluation.


Assuntos
Carcinoma de Células Escamosas/secundário , Fluordesoxiglucose F18/farmacologia , Linfonodos/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Neoplasias Penianas/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Carcinoma de Células Escamosas/diagnóstico , Seguimentos , Virilha , Humanos , Achados Incidentais , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Compostos Radiofarmacêuticos/farmacologia , Fatores de Tempo
11.
Cancer Imaging ; 21(1): 16, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482909

RESUMO

BACKGROUND: The use of PET/MRI for gynecological cancers is emerging. The purpose of this study was to assess the additional diagnostic value of PET over MRI alone in local and whole-body staging of cervical cancer, and to evaluate the benefit of standardized uptake value (SUV) and apparent diffusion coefficient (ADC) in staging. METHODS: Patients with histopathologically-proven cervical cancer and whole-body 18F-FDG PET/MRI obtained before definitive treatment were retrospectively registered. Local tumor spread, nodal involvement, and distant metastases were evaluated using PET/MRI or MRI dataset alone. Histopathology or clinical consensus with follow-up imaging were used as reference standard. Tumor SUVmax and ADC were measured and SUVmax/ADC ratio calculated. Area under the curve (AUC) was determined to predict diagnostic performance and Mann-Whitney U test was applied for group comparisons. RESULTS: In total, 33 patients who underwent surgery (n = 23) or first-line chemoradiation (n = 10) were included. PET/MRI resulted in higher AUC compared with MRI alone in detecting parametrial (0.89 versus 0.73), vaginal (0.85 versus 0.74), and deep cervical stromal invasion (0.96 versus 0.74), respectively. PET/MRI had higher diagnostic confidence than MRI in identifying patients with radical cone biopsy and no residual at hysterectomy (sensitivity 89% versus 44%). PET/MRI and MRI showed equal AUC for pelvic nodal staging (both 0.73), whereas AUC for distant metastases was higher using PET/MRI (0.80 versus 0.67). Tumor SUVmax/ADC ratio, but not SUVmax or ADC alone, was significantly higher in the presence of metastatic pelvic lymph nodes (P < 0.05). CONCLUSIONS: PET/MRI shows higher accuracy than MRI alone for determining local tumor spread and distant metastasis emphasizing the added value of PET over MRI alone in staging of cervical cancer. Tumor SUVmax/ADC ratio may predict pelvic nodal involvement.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Padrões de Referência
12.
Ann Otol Rhinol Laryngol ; 130(4): 424-428, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32847383

RESUMO

BACKGROUND: The inverted and oncocytic subtypes of sinonasal Schneiderian papillomas are benign tumors with possible rare malignant transformation and are typically managed with complete surgical resection and close follow-up. While computed tomography (CT) and magnetic resonance imaging (MRI) are mainstays in preoperative evaluation of bony invasion and soft tissue extension of the lesion, their imaging characteristics by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is less well characterized. OBJECTIVE: To describe the clinical presentation and management of a PET positive sinonasal lesion. To conduct a literature review of FDG uptake in benign sinonasal papillomas. METHODS: Case report (n = 1) and literature review of similar cases (n = 32). RESULTS: We report the case of a 69-year-old man presenting with an isolated left maxillary sinus mass with avid FDG uptake, discovered on PET/CT imaging. An endoscopic left maxillary mega-antrostomy provided successful definitive treatment for final pathologic diagnosis of oncocytic papilloma. Literature review of cases of sinonasal papillomas with avid FDG uptake found that oncocytic papillomas, on average, exhibit greater uptake than inverted papillomas and both may be mistaken as malignancies on PET. CONCLUSION: While PET imaging demonstrating avid FDG uptake is associated with an increased risk of malignancy, it does not rule out the possibility of a benign sinonasal papilloma nor other benign inflammatory lesions. Particularly, oncocytic papillomas may have very high FDG uptake and mimic malignant lesions.


Assuntos
Adenoma Oxífilo , Fluordesoxiglucose F18/farmacologia , Neoplasias do Seio Maxilar , Mucosa Nasal , Neoplasias/diagnóstico por imagem , Papiloma Invertido , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adenoma Oxífilo/diagnóstico por imagem , Adenoma Oxífilo/patologia , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias do Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/patologia , Mucosa Nasal/diagnóstico por imagem , Mucosa Nasal/patologia , Papiloma Invertido/diagnóstico por imagem , Papiloma Invertido/patologia , Cuidados Pré-Operatórios/métodos , Compostos Radiofarmacêuticos/farmacologia
14.
BMJ Case Rep ; 13(9)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32912884

RESUMO

A 54-year-old man presented with easy fatiguability, dyspnoea on exertion and dyspeptic symptoms. On evaluation, he was found to have an ulcero-proliferative growth in the gastric fundus, the biopsy of which was malignant melanoma of the stomach. Further evaluation with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) scan showed operable disease with no focus of disease elsewhere. He was diagnosed as primary gastric melanoma and underwent radical total gastrectomy with adequate margins. His postoperative period was uneventful. Further adjuvant therapy was refused by the patient. At 6-month follow-up, an 18F-FDG PET-CT scan was done, which showed no evidence of disease. On follow-up at 1-year, he was alive and asymptomatic.


Assuntos
Gastrectomia/métodos , Gastroscopia/métodos , Melanoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Gástricas , Biópsia/métodos , Diagnóstico Diferencial , Dispepsia/diagnóstico , Dispepsia/etiologia , Dispneia/diagnóstico , Dispneia/etiologia , Fadiga/diagnóstico , Fadiga/etiologia , Fluordesoxiglucose F18/farmacologia , Humanos , Masculino , Melanoma/patologia , Melanoma/fisiopatologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos/farmacologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
15.
JAMA Cardiol ; 5(9): 1000-1005, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936270

RESUMO

Importance: Myocardial replacement fibrosis has been reported to occur in one-third of patients with mitral valve prolapse (MVP) and significant mitral regurgitation (MR). However, it remains unknown whether there are detectable changes in myocardial metabolism suggestive of inflammation or ischemia that accompany the development of fibrosis. Objectives: To characterize the burden and distribution of fluorine 18-labeled (18F) fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) in patients with degenerative MVP and ventricular ectopy. Design, Setting, and Participants: Prospective observational study of 20 patients with MVP and significant primary degenerative MR who were referred for mitral valve repair and underwent hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Ventricular arrhythmias were categorized as either complex (n = 12) or minor (n = 8). Coregistered hybrid 18F FDG-PET and MRI LGE images were assessed and categorized. Recruitment occurred in the new patient clinic of a mitral valve repair reference center. This study was conducted from January 11, 2018, to June 26, 2019. Exposures: Simultaneous cardiac 18F FDG-PET and MRI with LGE imaging on a hybrid PET/MRI system and ambulatory rhythm monitoring. Main Outcomes and Measures: Patients were categorized by the presence and pattern of FDG uptake and LGE, the severity of ventricular arrhythmias, and the indication for mitral valve surgery. Results: In the cohort of 20 patients, the median age was 59.5 years (interquartile range, 52.5-63.2 years). Focal, or focal-on-diffuse uptake, of 18F-FDG (PET positive) was detected in 17 of 20 patients (85%). The FDG uptake coexisted with areas of LGE (PET/MRI positive) in 14 patients (70%). Of the 5 asymptomatic patients with normal ventricular indices and absence of any surgical indications, all were PET/MRI positive. Conclusions and Relevance: In this pilot study, we demonstrate a novel association between degenerative MVP and FDG uptake, a surrogate for myocardial inflammation and/or ischemia. Such evidence of myocardial injury, even in asymptomatic patients, suggests an ongoing subclinical disease process. These findings warrant further investigation into whether imaging for myocardial inflammation, ischemia, and scar has a role in arrhythmic risk stratification and whether it provides incremental prognostic value in patients with chronic severe mitral regurgitation undergoing active surveillance.


Assuntos
Arritmias Cardíacas/etiologia , Imagem Cinética por Ressonância Magnética/métodos , Prolapso da Valva Mitral/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Arritmias Cardíacas/diagnóstico , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Prolapso da Valva Mitral/complicações , Projetos Piloto , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes
16.
J Clin Invest ; 130(11): 6034-6040, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32780721

RESUMO

Air pollution involving particulate matter smaller than 2.5 µm in size (PM2.5) is the world's leading environmental risk factor contributing to mortality through cardiometabolic pathways. In this study, we modeled early life exposure using chow-fed C57BL/6J male mice that were exposed to real-world inhaled, concentrated PM2.5 (~10 times ambient levels/~60-120 µg/m3) or filtered air over a 14-week period. We investigated the effects of PM2.5 on phenotype, the transcriptome, and chromatin accessibility and compared these with the effects of a prototypical high-fat diet (HFD) as well as cessation of exposure on phenotype reversibility. Exposure to PM2.5 impaired glucose and insulin tolerance and reduced energy expenditure and 18FDG-PET uptake in brown adipose tissue. Multiple differentially expressed gene clusters in pathways involving metabolism and circadian rhythm were noted in insulin-responsive tissues. Although the magnitude of transcriptional change detected with PM2.5 exposure was lower than that observed with a HFD, the degree of alteration in chromatin accessibility after PM2.5 exposure was significant. The novel chromatin remodeler SMARCA5 (SWI/SNF complex) was regulated in response to PM2.5 exposure, the cessation of which was associated with a reversal of insulin resistance and restoration of chromatin accessibility and nucleosome positioning near transcription start sites, as well as a reversal of exposure-induced changes in the transcriptome, including SMARCA5. These changes indicate pliable epigenetic control mechanisms following cessation of exposure.


Assuntos
Tecido Adiposo Marrom , Poluentes Atmosféricos/toxicidade , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Resistência à Insulina , Adenosina Trifosfatases/metabolismo , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Animais , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Proteínas Cromossômicas não Histona/metabolismo , Fluordesoxiglucose F18/farmacologia , Camundongos , Tomografia por Emissão de Pósitrons , Transcriptoma/efeitos dos fármacos
17.
BMJ Case Rep ; 13(6)2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32522725

RESUMO

We present a 49-year-old woman with a history of an unresectable nasopharyngeal small cell carcinoma (SCC) who was treated with concurrent chemotherapy and radiation therapy. On surveillance positron emission tomography scan 14 months after diagnosis, her primary tumour appeared stable, but there was fludeoxyglucose uptake in the pancreas. A CT scan demonstrated a 3.4×2.1 cm ill-defined soft tissue mass at the tail of the pancreas, which was concerning for adenocarcinoma. However, further workup including endoscopic ultrasound and fine needle aspiration confirmed the mass to be a metastasis from her nasopharyngeal SCC. Because there have been no previously reported cases of a metastatic small cell carcinoma to the pancreas, there are no data about prognosis. Thus treatment options were tailored to the patient. Distal pancreatectomy, splenectomy and cholecystectomy were performed. The patient recovered from surgery without complication.


Assuntos
Carcinoma de Células Pequenas , Nasofaringe , Pâncreas , Pancreatectomia/métodos , Neoplasias Pancreáticas , Neoplasias Faríngeas , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/terapia , Quimiorradioterapia/métodos , Colecistectomia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Pessoa de Meia-Idade , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Estadiamento de Neoplasias , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/terapia , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Radiofarmacêuticos/farmacologia , Esplenectomia/métodos
18.
Oral Oncol ; 107: 104750, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32361565

RESUMO

OBJECTIVES: Pre- and post-treatment 18F-FDG PET/CT may have a prognostic role in human cancers. 18F-FDG PET/CT after primary surgery for head and neck cancer might also predict survival. Therefore, we evaluated the prognostic value of post-treatment 18F-FDG PET/CT in primary surgical patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also had 18F-FDG PET/CT scanning at a median 6 months after surgery. Post-treatment 18F-FDG PET/CT was considered positive, based on interpretation by experienced nuclear medicine physicians with integrating clinical information. Positive and negative predictive values (PPV and NPV) for positive 18F-FDG PET/CT in association with recurrence were calculated. Predictors for positive post-treatment 18F-FDG PET/CT were evaluated using binary logistic regression. Survival analysis was performed using Cox proportional hazard regression analysis. RESULTS: PPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P < 0.001). Five-year overall survival rates for patients with positive and negative PET/CT were 48.1% and 92.3%, respectively. Corresponding 5-year disease-free survival rates were 22.5% and 82.4%, respectively. Perineural invasion, positive resection margin, positive pathological node, and extranodal extension were the independent predictors of positive 18F-FDG PET/CT (all P < 0.05). CONCLUSIONS: Post-treatment 18F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Análise de Sobrevida , Adulto Jovem
20.
Can J Cardiol ; 36(6): 967.e17-967.e19, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32389686

RESUMO

This is a case report of a patient presenting an extremely rare cardiac malignancy: malignant peripheral nerve sheath tumour. The 18F-fluorodeoxyglucosis positron emission tomography associated to computed tomography (18F-FDG PET/CT) accesses the tumour anatomy and metabolic activity, thereby making it possible to characterize a malignant neoplasm noninvasively. The diagnostic approach with 18F-FDG PET/CT spared the heart from a likely futile invasive procedure when detecting a distant metastasis and changed the biopsy site and therapeutic planning.


Assuntos
Neoplasias Cardíacas , Septos Cardíacos , Neurofibrossarcoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada por Raios X/métodos , Tratamento Farmacológico/métodos , Ecocardiografia/métodos , Eletrocardiografia/métodos , Evolução Fatal , Fluordesoxiglucose F18/farmacologia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/fisiopatologia , Neoplasias Cardíacas/terapia , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neurofibrossarcoma/diagnóstico , Neurofibrossarcoma/patologia , Neurofibrossarcoma/fisiopatologia , Neurofibrossarcoma/terapia , Compostos Radiofarmacêuticos/farmacologia
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