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1.
J Nucl Med ; 65(4): 617-622, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38485275

RESUMO

The use of [18F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [18F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods: We recruited 18 patients with fILD awaiting lung biopsy for [18F]FDG PET/CT. We derived a target-to-background ratio (TBR) of maximum pulmonary uptake of [18F]FDG (SUVmax) divided by the lung background (SUVmin). Consecutive paraffin-embedded lung biopsy sections were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD) (CD31 and CD105/endoglin), and glucose transporter 1. MVD was expressed as vessel area percentage per high-power field (Va%/hpf). Differences in imaging and angiogenesis markers between histologic usual interstitial pneumonia (UIP) and non-UIP were assessed using a nonparametric Mann-Whitney test. Correlation of imaging with angiogenesis markers was assessed using the nonparametric Spearman rank correlation. Univariate Kaplan-Meier survival analysis assessed the difference in the survival curves for each of the angiogenesis markers (separated by their respective optimal cutoff) using the log-rank test. Statistical analysis was performed using SPSS. Results: In total, 18 patients were followed for an average of 41.36 mo (range, 5.69-132.46 mo; median, 30.07 mo). Only CD105 MVD showed a significantly positive correlation with [18F]FDG TBR (Spearman rank correlation, 0.556; P < 0.05, n = 13). There was no correlation between [18F]FDG uptake and macrophage expression of glucose transporter 1. CD105 and CD31 were higher for UIP than for non-UIP, with CD105 reaching statistical significance (P = 0.011). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with CD105 MVD of less than 12 Va%/hpf or CD31 MVD of less than 35 Va%/hpf had a significantly better prognosis (no deaths during follow-up in the case of CD105) than did patients with higher scores of CD105 MVD (median survival, 35 mo; P = 0.041, n = 13) or CD31 MVD (median survival, 28 mo; P = 0.014, n = 13). Conclusion: Previous work has used [18F]FDG uptake in PET/CT as a biomarker in fILD. Here, we highlight a correlation between angiogenesis and [18F]FDG TBR. We show that MVD is higher for UIP than for non-UIP and is associated with mortality in patients with fILD. These data set the scene to investigate the potential role of vasculature and angiogenesis in fibrosis.


Assuntos
Doenças Pulmonares Intersticiais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Transportador de Glucose Tipo 1 , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Neovascularização Patológica/diagnóstico por imagem , Fibrose , Biomarcadores , Biópsia , Prognóstico
2.
Breast Dis ; 43(1): 19-23, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38489166

RESUMO

INTRODUCTION: Chemotherapy is conventionally offered to non-stage IV breast cancer patients with metastatic nodes. However, the RxPONDER trial showed that chemotherapy can be omitted in selected patients with 1-3 metastatic nodes if the 21-gene assay recurrence score is ≤25. We aimed to investigate if axillary ultrasound can identify this group of patients with limited nodal burden so that they can undergo upfront surgery followed by gene assay testing, to potentially avoid chemotherapy. METHODS: T1-3, node positive, hormone receptor-positive and HER2-negative breast cancer patients ≥50 years old with axillary lymph node dissection (ALND) were reviewed from 2 centres. Patients with neoadjuvant chemotherapy and bilateral cancers were excluded. Number of ultrasound-detected abnormal axillary nodes, demographic and histological parameters were correlated with the number of metastatic nodes found on ALND. RESULTS: 138 patients were included, 59 (42.8%) and 79 (57.2%) patients had 1-3 and >3 metastatic nodes on ALND respectively. On logistic regression and ROC analysis, the number of ultrasound-detected abnormal nodes was significant (p < 0.001) for predicting limited nodal burden (ROC AUC = 0.7135). Probabilities of <4 metastatic nodes with ultrasound cut-offs of 5, 6 and 8 abnormal nodes were 0.057, 0.026 and 0.005 respectively, with 100% specificity. CONCLUSION: A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients.


Assuntos
Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Biópsia de Linfonodo Sentinela , Metástase Linfática , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Excisão de Linfonodo , Genômica , Axila/patologia , Terapia Neoadjuvante
3.
Mol Cell Biochem ; 478(2): 393-406, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35836027

RESUMO

Novel derivatives of aminophenyl-1,4-naphthoquinones, in which a pyrrolidine group was added to the naphthoquinone ring, were synthesized and investigated for the mechanisms of leukemic cell killing. The novel compounds, TW-85 and TW-96, differ in the functional (methyl or hydroxyl) group at the para-position of the aminophenyl moiety. TW-85 and TW-96 were found to induce concentration- and time-dependent apoptotic and/or necrotic cell death in human U937 promonocytic leukemia cells but only TW-96 could also kill K562 chronic myeloid leukemia cells and CCRF-CEM lymphoblastic leukemia cells. Normal peripheral blood mononuclear cells were noticeably less responsive to both compounds than leukemia cells. At low micromolar concentrations used, TW-85 killed U937 cells mainly by inducing apoptosis. TW-96 was a weaker apoptotic agent in U937 cells but proved to be cytotoxic and a stronger inducer of necrosis in all three leukemic cell lines tested. Both compounds induced mitochondrial permeability transition pore opening, cytochrome c release, and caspase activation in U937 cells. Cytotoxicity induced by TW-96, but not by TW-85, was associated with the elevation of the cytosolic levels of reactive oxygen species (ROS). The latter was attenuated by diphenyleneiodonium, indicating that NADPH oxidase was likely to be the source of ROS generation. Activation of p38 MAPK by the two agents appeared to prevent necrosis but differentially affected apoptotic cell death in U937 cells. These results further expand our understanding of the structure-activity relationship of aminophenyl-1,4-naphthoquinones as potential anti-leukemic agents with distinct modes of action.


Assuntos
Leucemia Mieloide , Leucemia , Naftoquinonas , Humanos , Naftoquinonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Leucócitos Mononucleares/metabolismo , Morte Celular , Apoptose , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Células U937 , Necrose
5.
Breast Dis ; 41(1): 535-543, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36683492

RESUMO

BACKGROUND: Tissue markers are inserted into the breast after percutaneous biopsy to mark the site of the lesion to facilitate potential re-localisation. Tissue markers are increasingly developed with improved sonographic visibility due to benefits conferred by ultrasound-guided localisation. OBJECTIVES: We aim to study the sonographic visibility of the recently-introduced UltracorTM TwirlTM tissue marker and feasibility of its pre-operative localisation under ultrasound guidance. METHODS: All patients who underwent insertion of the UltracorTM TwirlTM tissue marker in our institution from July 2017 to December 2018 were reviewed. Retrospective data including sonographic visibility, evidence of migration and rate of successful surgical excision were collected. RESULTS: All tissue markers were visible on subsequent ultrasound with 198 (85.0%) well-visualised with high degree of confidence while 35 (15.0%) were moderately well-visualised with moderate level of confidence. None of the tissue markers were poorly visualised and none demonstrated migration. No statistical difference in sonographic visibility is seen based on interval duration between deployment and subsequent ultrasound assessment or depth of tissue marker. CONCLUSION: UltracorTM TwirlTM demonstrates consistent sonographic visibility, identifiable with a high or moderate level of confidence with no associated migration. Its use in pre-operative localisation with ultrasound guidance is therefore both reliable and feasible.


Assuntos
Neoplasias da Mama , Ultrassonografia Mamária , Feminino , Humanos , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Ultrassonografia , Mama/diagnóstico por imagem , Mama/cirurgia , Mama/patologia
7.
Int J Qual Health Care ; 33(1)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33306102

RESUMO

OBJECTIVE: To explore differences in position emission tomography-computed tomography (PET-CT) service provision internationally to further understand the impact variation may have upon cancer services. To identify areas of further exploration for researchers and policymakers to optimize PET-CT services and improve the quality of cancer services. DESIGN: Comparative analysis using data based on pre-defined PET-CT service metrics from PET-CT stakeholders across seven countries. This was further informed via document analysis of clinical indication guidance and expert consensus through round-table discussions of relevant PET-CT stakeholders. Descriptive comparative analyses were produced on use, capacity and indication guidance for PET-CT services between jurisdictions. SETTING: PET-CT services across 21 jurisdictions in seven countries (Australia, Denmark, Canada, Ireland, New Zealand, Norway and the UK). PARTICIPANTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULTS: PET-CT service provision has grown over the period 2006-2017, but scale of increase in capacity and demand is variable. Clinical indication guidance varied across countries, particularly for small-cell lung cancer staging and the specific acknowledgement of gastric cancer within oesophagogastric cancers. There is limited and inconsistent data capture, coding, accessibility and availability of PET-CT activity across countries studied. CONCLUSIONS: Variation in PET-CT scanner quantity, acquisition over time and guidance upon use exists internationally. There is a lack of routinely captured and accessible PET-CT data across the International Cancer Benchmarking Partnership countries due to inconsistent data definitions, data linkage issues, uncertain coverage of data and lack of specific coding. This is a barrier in improving the quality of PET-CT services globally. There needs to be greater, richer data capture of diagnostic and staging tools to facilitate learning of best practice and optimize cancer services.


Assuntos
Benchmarking , Neoplasias , Austrália , Canadá , Humanos , Irlanda , Neoplasias/diagnóstico por imagem , Nova Zelândia , Noruega , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
9.
J Med Ultrasound ; 28(1): 44-47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368450

RESUMO

This case reports on a patient presenting with abdominal pain of 1-month duration; in whom, ultrasound (US) detected a colonic lipoma with intussusception. Further investigation with computed tomography confirmed this finding, and successful endoscopic removal of the lipoma was performed. This case highlights the importance of careful evaluation of the region of interest during US, knowing the appearance of lipoma on US and other modalities, thus aiding its adequate management.

11.
J Radiol Case Rep ; 13(10): 1-10, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32184921

RESUMO

We present a case of a 65 year old female with newly diagnosed primary peritoneal serous carcinoma who was found to have indeterminate segmental microcalcifications in the right upper outer quadrant with a mildly enlarged right axillary node on mammogram. There was no associated breast mass on ultrasound. Core biopsy of the right axillary lymph node and right upper outer quadrant breast microcalcifications confirmed the presence of breast metastases at both sites from primary peritoneal serous carcinoma. This case highlights the importance of histopathological correlation of any breast and axillary abnormalities in patient with primary extramammary malignancy. Imaging features of metastatic lesions to the breast are also reviewed.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Neoplasias da Mama/secundário , Calcinose/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/secundário , Neoplasias Peritoneais/patologia , Idoso , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Mamografia
12.
J Thorac Dis ; 10(8): 4806-4811, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30233853

RESUMO

BACKGROUND: Despite systematic investigation with computed tomography (CT), positron emission tomography (PET)/CT, CT or magnetic resonance imaging (MRI) brain imaging and supplementary investigation using endobronchial ultrasound guided biopsy (EBUS), endo-oesophageal ultrasound guided biopsy (EUS), fine needle aspiration (FNA), mediastinoscopy or mediastinotomy, there is an approximately 10% rate of occult N2 disease identified at pathological staging. It has been hypothesised that such occult disease, too small or inactive to be identified during pre-operative multi-modality staging, may represent low volume disease that may have equivalent survival to patients with similar stage at clinical, pre-operative assessment. We compared the long-term survival and disease-free survival of patients with the same clinical TNM stage with and without occult N2 disease. METHODS: We retrospectively analysed a database that prospectively captured information on all patients assessed and treated for lung cancer in our surgical unit. We reviewed data on patients who underwent lung cancer surgery with curative intent between January 2006 and August 2010. RESULTS: A total of 312 lung cancer resections were performed [mean age 68 (range, 42-86) years old and male:female ratio 1.14:1]. Occult N2 disease was identified in 28 (8.7%) of 312 patients. There was no difference in the rate of N2 disease for different tumour histological types. Five-year survival with occult N2 disease was 35.8% vs. 62.5% without. Median survival was 34 months with occult N2 disease vs. 84 months without. CONCLUSIONS: With contemporary staging techniques, so-called occult N2 disease, even with low volume and PET non-avid disease, does not have an indolent course and should still be considered a risk factor for poorer prognosis.

13.
Eur J Nucl Med Mol Imaging ; 45(5): 806-815, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29335764

RESUMO

PURPOSE: There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF. METHODS: A total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan-Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients. RESULTS: During a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald-Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data ("PET modified GAP score") refined the ability to predict mortality. CONCLUSIONS: A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Feminino , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Medição de Risco , Tomografia Computadorizada por Raios X
14.
Eur J Nucl Med Mol Imaging ; 42(1): 49-55, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25120040

RESUMO

PURPOSE: To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. METHODS: Fifty consecutive consenting patients who underwent routine (18)F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. RESULTS: ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). CONCLUSION: In lung cancer patients PET/MR appears to be a robust technique for preoperative staging.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Variações Dependentes do Observador , Período Pré-Operatório , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
15.
Eur J Nucl Med Mol Imaging ; 41(2): 337-42, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23942907

RESUMO

PURPOSE: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. METHODS: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent (18)F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of (18)F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). RESULTS: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). CONCLUSION: IPF patients have increased pulmonary uptake of (18)F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring.


Assuntos
Fluordesoxiglucose F18 , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Sensibilidade e Especificidade
16.
Clin Cancer Res ; 19(13): 3591-9, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23659970

RESUMO

PURPOSE: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. RESULTS: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0.001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment. CONCLUSIONS: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes
17.
Eur J Cardiothorac Surg ; 43(1): 104-9; discussion 109-10, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22529185

RESUMO

OBJECTIVES: Lung cancer staging has improved in recent years. Assuming that contemporary detailed preoperative staging may yield a lower rate of stage change after surgery, we were interested to determine the impact of our lymph node dissections performed at the time of surgical resection. METHODS: We retrospectively analysed a database in our surgical unit that prospectively captured information on all patients assessed and treated for lung cancer. We reviewed the data on patients who underwent lung cancer surgery with curative intent between January 2006 and August 2010 so as to reflect contemporary practice. Prior to potentially curative treatment, patients systematically underwent staging computerized tomography (CT), integrated positron emission tomography (PET) with CT and brain imaging. Enlarged and/or PET-positive nodes were subject to invasive evaluation to establish the nodal status in line with the current guidelines. This was performed by needle aspiration or biopsy usually with ultrasound guidance, endobronchial or endo-oesophageal ultrasound with needle biopsy; mediastinoscopy; mediastinotomy; video-assisted or open surgery. RESULTS: Three hundred and twelve lung cancer resections were performed (a mean age of 68 years [range 42-86] and a male-to-female ratio of 1.14:1). Despite thorough preoperative evaluations, 25.3% of patients had a change in nodal status after lung resection and lymph node dissection; of which 20.8% of patients had a nodal status upstaging. Occult N2 disease was identified in 31 (9.9%) of 312 patients. Patients with cT1 tumours showed a nodal upstaging of 12.3% compared with 25.3% in cT2 tumours. There was no difference in the rate of N2 disease for different tumour histological types. CONCLUSIONS: Despite systematic preoperative staging, there continues to be a high rate of nodal status change following surgical resection and lymph node dissection. If considering non-surgical treatments for the early stage lung cancer, the impact of this discrepancy should be considered. If not, errors in prognosis and in determining correct adjuvant treatment may arise.


Assuntos
Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Pneumonectomia , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Mol Imaging ; 11(5): 353-60, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22954179

RESUMO

We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for (18)F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of (18)F-FDG quantified on PET as the standardized uptake value (SUV(max)) assessed tumor metabolism. The median values for SUV(max) and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUV(max) versus size (rs  =  .40, p  =  .001) and SUV/PE versus size (r  =  .43, p < .001). Patients with earlier-stage (I-IIA, n  =  30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n  =  34) disease (p  =  .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p  =  .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p  =  .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p  =  .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Imagem Molecular/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Estudos Prospectivos , Estatísticas não Paramétricas
19.
Chem Biodivers ; 9(6): 1198-204, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22700237

RESUMO

One novel lavandulyl flavanone (=2,3-dihydro-2-phenyl-4H-1-benzopyran-4-one) with an unusual 5,2',4',6'-tetrahydroxy substitution, calycinigin A (1), was isolated from the stems of Hypericum calycinum L. (Hypericaceae). The structure was elucidated on the basis of 1D- and 2D-NMR analysis, as well as mass spectrometry (LR-EI- and HR-EI-MS) and circular dichroism. Three known lavandulyl flavanones with 5,7,2',4',6'-pentahydroxy substitution, i.e., 2-4, were also isolated. Chemosystematically, this is the first report on the occurrence of prenylated flavanones in the family Hypericaceae. Reduction of cell viability by all compounds was evaluated in a MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay using HeLa cells. Compound 1 showed moderate activity with an IC50 value of 9.7±1.8 µM, whereas compounds 2-4 were less active exhibiting IC50 values of 11.6±0.9, 19.3±1.5, and 40.7±2.4 µM, respectively. The antioxidant activity was evaluated by an ORAC (Oxygen Radical Absorbance Capacity) assay, and calycinigin A (1) was again the most active compound with a Trolox equivalent of 2.3±0.2. None of the compounds was able to reduce the TNF-α induced ICAM-1 expression in vitro using human microvascular endothelial cells (HMEC-1).


Assuntos
Flavanonas/química , Hypericum/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavanonas/toxicidade , Radicais Livres/química , Células HeLa , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Caules de Planta/química , Fator de Necrose Tumoral alfa/farmacologia
20.
Mol Imaging ; 11(2): 91-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22469237

RESUMO

We prospectively investigated the potential of positron emission tomography (PET) using the somatostatin receptor (SSTR) analogue 68Ga-DOTATATE and 2-deoxy-2[¹8F]fluoro-D-glucose (¹8F-FDG) in diffuse parenchymal lung disease (DPLD). Twenty-six patients (mean age 68.9 ± 11.0 years) with DPLD were recruited for 68Ga-DOTATATE and ¹8F-FDG combined PET/high-resolution computed tomography (HRCT) studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value [SUV(max)]) was calculated. The distribution of PET tracer was compared to the distribution of lung parenchymal changes on HRCT. All patients demonstrated increased pulmonary PET signal with 68Ga-DOTATATE and ¹8F-FDG. The distribution of parenchymal uptake was similar, with both tracers corresponding to the distribution of HRCT changes. The mean SUV(max) was 2.2 ± 0.7 for 68Ga-DOTATATE and 2.8 ± 1.0 (t-test, p  =  .018) for ¹8F-FDG. The mean 68Ga-DOTATATE SUV(max) in IPF patients was 2.5 ± 0.9, whereas it was 2.0 ± 0.7 (p  =  .235) in NSIP patients. The correlation between 68Ga-DOTATATE SUV(max) and gas transfer (transfer factor of the lung for carbon monoxide [TLCO]) was r  =  -.34 (p  =  .127) and r  =  -.49 (p  =  .028) between ¹8F-FDG SUV(max) and TLCO. We provide noninvasive in vivo evidence in humans showing that SSTRs may be detected in the lungs of patients with DPLD in a similar distribution to sites of increased uptake of ¹8F-FDG on PET.


Assuntos
Fluordesoxiglucose F18 , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Receptores de Somatostatina/metabolismo , Coloração e Rotulagem , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Masculino
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