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1.
Future Oncol ; : 1-8, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38861293

RESUMO

Treatment options for patients with biliary tract cancer are limited, and the prognosis is poor. CTX-009, a novel bispecific antibody targeting both DLL4 and VEGF-A, has demonstrated antitumor activity in patients with advanced cancers as both a monotherapy and in combination with chemotherapy. In a phase II study of patients with advanced biliary tract cancer who had received one or two prior therapies, CTX-009 with paclitaxel demonstrated a 37.5% overall response rate (ORR). Described here is the design of and rationale for COMPANION-002, a randomized phase II/III study, which will evaluate the safety and efficacy of CTX-009 in combination with paclitaxel versus paclitaxel alone as second-line treatment for patients with advanced biliary tract cancer. The primary end point is ORR, and crossover is allowed.Clinical Trial Registration: NCT05506943 (ClinicalTrials.gov).


Looking for new options for patients with advanced biliary tract cancer? Explore COMPANION-002, Compass Therapeutics' phase II/III study of CTX-009 + paclitaxel as a second line treatment.#CMPX #biotech #healthcare #rarecancer.

2.
Eur Radiol ; 31(3): 1578-1587, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32902745

RESUMO

OBJECTIVES: To compare liver stiffness measurement (LSM) provided by Canon 2D-shear wave elastography (2D-SWE) and transient elastography (TE), the latter being the reference method. METHODS: Prospective study conducted in four European centres from 2015 to 2016 including patients with various chronic liver diseases who had LSMs with both 2D-SWE and TE on the same day. Median of 10 valid measurements (in kPa) was used for comparison using paired t test, Pearson correlation, intraclass correlation coefficient (ICC) and Bland-Altman plot. The ability of 2D-SWE to stratify patient according to recognised LSM-TE thresholds was assessed by ROC curve analysis. RESULTS: Six hundred forty patients were scanned, where 593 (92.7%), 572 (89.4%) and 537 (83.9%) had reliable LSMs by TE, 2D-SWE and both combined, respectively. In the latter (n = 537, 310 [57.7%] male, mean 55.3 ± 14.8 years), median LSM-TE and LSM-2D-SWE had a mean of 10.1 ± 9.4 kPa (range 2.4-75) and 9.1 ± 6.1 kPa (range 3.6-55.7) (paired t test: p < 0.001), respectively. These were significantly correlated (Pearson r = 0.932, p < 0.001, ICC 0.850 (0.825-0.872), bias 0.99 ± 4.33 kPa [95% limits of agreement - 9.48 to + 7.49] with proportional error towards higher LSM values). LSM-2D-SWE values significantly increased with TE categories (ANOVA: p < 0.001). AUROCs ranged from 0.935 ± 0.010 (95% CI 0.910-0.954) to 0.973 ± 0.009 (95% CI 0.955-0.985), resulting in correct classification of 390/537 (73%) patients. Three 2D-SWE measurements were sufficient for reliable LSMs. CONCLUSION: LSM using 2D-SWE correlates well with TE. It tends to underestimate higher stages of liver fibrosis but correctly classifies the majority of patients. It may be used in TE-derived algorithms to manage patients. KEY POINTS: • Liver stiffness measurement (LSM) by 2D-shear wave elastography (2D-SWE) and transient elastography (TE) are strongly correlated. • 2D-SWE shows proportionately lower LSM values compared to TE, particularly with the higher LSM range. • Three individual measurements by 2D-SWE are sufficient to assess LSM reliably.


Assuntos
Técnicas de Imagem por Elasticidade , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes
3.
Chemistry ; 26(17): 3661-3687, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-31709642

RESUMO

The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.


Assuntos
Racemases e Epimerases/química , Albumina Sérica/química , Cinética , Estereoisomerismo
4.
Future Oncol ; 16(16): 1069-1081, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32374623

RESUMO

Gemcitabine/cisplatin is standard of care for first-line treatment of patients with advanced biliary tract cancer (aBTC); new treatments are needed. NUC-1031 is designed to overcome key cancer resistance mechanisms associated with gemcitabine. The tolerability/efficacy signal of NUC-1031/cisplatin in the Phase Ib ABC-08 study suggested that this combination may represent a more efficacious therapy than gemcitabine/cisplatin for patients with aBTC, leading to initiation of the global NuTide:121 study which will include 828 patients ≥18 years with untreated histologically/cytologically-confirmed aBTC (including cholangiocarcinoma, gallbladder or ampullary cancer); randomized (1:1) to NUC-1031 (725 mg/m2)/cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2)/cisplatin (25 mg/m2), on days 1/8, Q21-days. Primary objectives are overall survival and objective response rate. Secondary objectives: progression-free survival, safety, pharmacokinetics, patient-reported quality of life and correlative studies. (Investigational new drug (IND) number: 139058, European Clinical Trials database: EudraCT Number 2019-001025-28, ClinicalTrials.gov identifier: NCT04163900).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ductos Biliares Intra-Hepáticos/efeitos dos fármacos , Neoplasias do Sistema Biliar/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias do Sistema Biliar/patologia , Colangiocarcinoma/patologia , Cisplatino/administração & dosagem , Monofosfato de Citidina/administração & dosagem , Monofosfato de Citidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem , Gencitabina
5.
J Chem Inf Model ; 59(1): 98-116, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30462505

RESUMO

A framework is presented for the calculation of novel alignment-free descriptors of molecular shape. The methods are based on the technique of spectral geometry which has been developed in the field of computer vision where it has shown impressive performance for the comparison of deformable objects such as people and animals. Spectral geometry techniques encode shape by capturing the curvature of the surface of an object into a compact, information-rich representation that is alignment-free while also being invariant to isometric deformations, that is, changes that do not distort distances over the surface. Here, we adapt the technique to the new domain of molecular shape representation. We describe a series of parametrization steps aimed at optimizing the method for this new domain. Our focus here is on demonstrating that the basic approach is able to capture a molecular shape into a compact and information-rich descriptor. We demonstrate improved performance in virtual screening over a more established alignment-free method and impressive performance compared to a more accurate, but much more computationally demanding, alignment-based approach.


Assuntos
Processamento de Imagem Assistida por Computador , Estrutura Molecular , Algoritmos , Simulação por Computador , Bases de Dados de Compostos Químicos , Modelos Moleculares
6.
J Chem Inf Model ; 58(4): 747-760, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29600850

RESUMO

We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay between two molecules and thus to obtain improved overlaps as judged by an increase in calculated similarity values. ReFlex3D is open-source and built as a python package working in combination with the OEChem Toolkit. As such it can readily be implemented in existing workflows ranging from the selection of compounds from a virtual screening campaign to the construction of similarity based prediction models to estimate binding affinities. We evaluate ReFlex3D against the AstraZeneca Validation Test Set and illustrate its potential within a predictive model compared to an established method (Posit).


Assuntos
Algoritmos , Modelos Moleculares , Eletricidade Estática , Cristalografia por Raios X , Conformação Molecular , Linguagens de Programação
9.
Angew Chem Int Ed Engl ; 57(4): 982-985, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29072355

RESUMO

Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1 H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second-order rate constants for general-base-catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.

10.
AJR Am J Roentgenol ; 208(2): 446-452, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27959665

RESUMO

OBJECTIVE: Because of concern over medical ionizing radiation exposure of children, contrast-enhanced ultrasound (CEUS) has generated interest as an inexpensive, ionizing radiation-free alternative to CT and MRI. CEUS has received approval for pediatric hepatic use but remains off-label for a range of other applications. The purposes of this study were to retrospectively analyze adverse incidents encountered in pediatric CEUS and to assess the financial benefits of reducing the number of CT and MRI examinations performed. MATERIALS AND METHODS: All pediatric (patients 18 years and younger) CEUS examinations performed between January 2008 and December 2015 were reviewed. All immediate reactions deemed due to contrast examinations were documented in radiology reports. Electronic patient records were examined for adverse reactions within 24 hours not due to an underlying pathologic condition. With tariffs from the U.K. National Institute of Clinical Excellence analysis, CEUS utilization cost ($94) was compared with the CT ($168) and MRI ($274) costs of the conventional imaging pathway. RESULTS: The records of 305 pediatric patients (187 boys, 118 girls; age range, 1 month-18 years) undergoing CEUS were reviewed. Most of the studies were for characterizing liver lesions (147/305 [48.2%]) and trauma (113/305 [37.1%]); the others were for renal, vascular, and intracavitary assessment (45/305 [14.8%]). No immediate adverse reactions occurred. Delayed adverse reactions occurred in two patients (2/305 [0.7%]). These reactions were transient hypertension and transient tachycardia. Neither was symptomatic, and both were deemed not due to the underlying disorder. The potential cost savings of CEUS were $74 per examination over CT and $180 over MRI. CONCLUSION: Pediatric CEUS is a safe and potentially cost-effective imaging modality. Using it allows reduction in the ionizing radiation associated with CT and in the gadolinium contrast administration, sedation, and anesthesia sometimes required for MRI.


Assuntos
Análise Custo-Benefício/economia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/economia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Pediatria/economia , Ultrassonografia/economia , Adolescente , Criança , Pré-Escolar , Meios de Contraste/economia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Ultrassonografia/estatística & dados numéricos , Reino Unido/epidemiologia
11.
J Chem Inf Model ; 57(7): 1703-1714, 2017 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-28653850

RESUMO

Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a set of 16 structurally similar compounds was assembled and investigated. Successfully, in vitro measurements revealed one compound, 5-(4-piperidyl)isothiazol-3-ol, superior in potency compared to the initial lead. Furthermore, a strikingly high correlation (R2 = 0.93) between anti-fibrinolytic activity and kringle 1 binding affinity provided strong support for the hypothesized inhibition mechanism, as well as revealing opportunities to fine-tune biological effects through minor structural modifications. Several different ligand-based (Freeform, shape, and electrostatic-based similarities) and structure-based methods (e.g., Posit, MM/GBSA, FEP+) were used to retrospectively predict the binding affinities. A combined method, molecular alignment using Posit and scoring with Tcombo, lead to the highest coefficient of determination (R2 = 0.6).


Assuntos
Antifibrinolíticos/química , Antifibrinolíticos/farmacologia , Descoberta de Drogas , Fibrinolisina/antagonistas & inibidores , Isoxazóis/química , Isoxazóis/farmacologia , Piperidinas/química , Piperidinas/farmacologia , Antifibrinolíticos/metabolismo , Fibrinolisina/química , Fibrinolisina/metabolismo , Isoxazóis/metabolismo , Simulação de Acoplamento Molecular , Piperidinas/metabolismo , Domínios Proteicos , Relação Quantitativa Estrutura-Atividade , Termodinâmica
12.
J Ultrasound Med ; 36(9): 1943-1954, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28626910

RESUMO

Pediatric pneumonia can be complicated by necrotizing pneumonia or a parapneumonic effusion either in the form of an empyema or a clear effusion. Ultrasonography (US) and computed tomography represent well-established modalities for evaluation of complicated pediatric pneumonia. Contrast-enhanced ultrasound (CEUS) was recently introduced and is gaining increasing acceptance in pediatric imaging. In this case series, we present our initial experience with both intravenous and intracavitary use of CEUS in children with complicated pneumonia. Intravenous CEUS accurately and confidently showed necrotizing pneumonia and delineated pleural effusions, whereas intracavitary CEUS accurately identified the chest catheter location and patency and showed the presence of loculations, suggesting the use of fibrinolytics.


Assuntos
Meios de Contraste/administração & dosagem , Aumento da Imagem/métodos , Pneumonia/diagnóstico por imagem , Ultrassonografia/métodos , Administração Intravenosa , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Pulmão/diagnóstico por imagem , Masculino , Variações Dependentes do Observador , Cavidade Pleural/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
Ultraschall Med ; 38(4): 377-394, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28407654

RESUMO

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias , Humanos , Hepatopatias/diagnóstico por imagem , Cintilografia , Ultrassonografia
14.
Ultraschall Med ; 38(4): e16-e47, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28407655

RESUMO

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts. The second part provides clinical information about the practical use of elastography equipment and the interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias , Artefatos , Humanos , Hepatopatias/diagnóstico por imagem , Ultrassonografia
15.
J Cancer Educ ; 32(3): 496-502, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26768145

RESUMO

Trainee exposure to clinical oncology during residency training is heterogeneous and often modest. The steep learning curve upon entry into fellowship can result in undue stress for fellows and their patients. Simulation-based training has been shown to be superior to classical didactic approaches. We have introduced several innovative simulation-based workshops into the curriculum for the Johns Hopkins Hematology/Oncology Fellowship Training Program in order to address this unmet need. During the first months of training, fellows were engaged in activities emphasizing essential clinical and procedural skills. Specific workshops included the following: (1) chemotherapy writing, (2) cadaveric and simulation-based bone marrow biopsy and intrathecal chemotherapy administration, and (3) simulation-based communication skills training. All first-year fellows in our program participated in these exercises. Pre- and post-workshop surveys were administered to assess knowledge, attitudes, and behaviors; additional distant post-workshop evaluations were disseminated to assess the durability/impact of the curricula and for program evaluation. Overall, participating fellows indicated that the workshops improved patient care and comfort with procedures and patient-centered communication. Continued implementation of these workshops was recommended for program improvement. To the best of our knowledge, ours is amongst the first oncology fellowship training programs to systematically implement simulation-based curricula into our schema for fellowship training. We hypothesize that proactively introducing fellows to these high-yield activities will translate into improved patient care and reduced stress for trainees. Additional investigation into the long-term impact of such curricula remains an area of ongoing need.


Assuntos
Currículo , Bolsas de Estudo , Hematologia/educação , Oncologia/educação , Treinamento por Simulação/métodos , Comunicação , Educação de Pós-Graduação em Medicina , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários
16.
Radiology ; 277(2): 594-603, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26069923

RESUMO

PURPOSE: To determine the efficacy of combined continuous sorafenib therapy and drug-eluting bead (DEB) transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Inclusion criteria included unresectable HCC, a treatment naïve status, an Eastern Cooperative Oncology Group score of 0-1, and a Child-Pugh score of A-B7. Continuous sorafenib therapy (400 mg twice daily) was started 1 week before the first round of DEB TACE, which was performed in 6-week cycles. Up to four rounds of DEB TACE therapy were allowed on demand within 6 months. The primary end point was safety. Secondary end points were time to progression (TTP), response rate, and overall survival (OS) and were stratified by the Barcelona Clinic Liver Cancer (BCLC) stage and the duration of sorafenib therapy. OS was assessed with Kaplan-Meier estimates, and the Mantel-Cox log-rank test was used to determine differences in survival. A two-sided P value of less than .05 was considered to indicate a significant difference. The study was approved by the Johns Hopkins institutional review board and remained open from March 2009 to January 2012. RESULTS: Fifty patients--of whom 76% were male, 92% had a Child-Pugh score of A, and 62% had BCLC stage C disease--underwent a median of three cycles of therapy. The 6-month disease control rate (defined as complete response plus partial response plus stable disease) was 94% according to the response evaluation criteria in solid tumors. Median TTP and OS were 13.9 and 20.4 months, respectively, and 81% of toxicities were grades 1-2. There was one death that was possibly treatment related. CONCLUSION: Combined continuous sorafenib therapy and on-demand DEB TACE provided excellent local disease control and did not lead to multiplicative toxicities. Long-term administration of sorafenib therapy in combination with DEB TACE may have a survival benefit in patients with advanced HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Meios de Contraste , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Sorafenibe , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
17.
Eur Radiol ; 25(2): 380-90, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25226843

RESUMO

OBJECTIVE: To prospectively assess treatment response using volumetric functional magnetic resonance imaging (MRI) metrics in patients with hepatocellular carcinoma (HCC) treated with the combination of doxorubicin-eluting bead-transarterial chemoembolization (DEB TACE) and sorafenib. METHODS: A single center study enrolled 41 patients treated with systemic sorafenib, 400 mg twice a day, combined with DEB TACE. All patients had a pre-treatment and 3-4 week post-treatment MRI. Anatomic response criteria (RECIST, mRECIST and EASL) and volumetric functional response (ADC, enhancement) were assessed. Statistical analyses included paired Student's t-test, Kaplan-Meier curves, Cohen's Kappa, and multivariate cox proportional hazard model. RESULTS: Median tumour size by RECIST remained unchanged post-treatment (8.3 ± 4.1 cm vs. 8.1 ± 4.3 cm, p = 0.44). There was no significant survival difference for early response by RECIST (p = 0.93). EASL and mRECIST could not be analyzed in 12 patients. Volumetric ADC increased significantly (1.32 × 10(-3) mm(2)/sec to 1.60 × 10(-3) mm(2)/sec, p < 0.001), and volumetric enhancement decreased significantly in HAP (38.2% to 17.6%, p < 0.001) and PVP (76.6% to 41.2%, p < 0.005). Patients who demonstrated ≥ 65% decrease PVP enhancement had significantly improved overall survival compared to non-responders (p < 0.005). CONCLUSION: Volumetric PVP enhancement was demonstrated to be significantly correlated with survival in the combination of DEB TACE and sorafenib for patients with HCC, enabling precise stratification of responders and non-responders. KEY POINTS: • PVP enhancement is significantly correlated with survival in responders (p < 0.005). • There was no significant survival difference for early response using RECIST (p = 0.93). • mRECIST or EASL could not assess tumour response in 29% of patients.


Assuntos
Carcinoma Hepatocelular/patologia , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sorafenibe , Taxa de Sobrevida/tendências , Fatores de Tempo , Carga Tumoral
18.
Cancer Treat Res ; 164: 195-219, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25677025

RESUMO

The benefits of applying comparative effectiveness research (CER) strategies to the management of cancer are important. As the incidence of cancer increases both in the United States and worldwide, accurate analysis of which tests and treatments should be applied in which situations is critical, both in terms of measurable and meaningful clinical outcomes and health care costs. In the last 20 years alone, multiple controversies have arisen in the diagnosis and treatment of primary and metastatic tumors of the liver, making the management of liver malignancies a prime example of CER. Contributing factors to the development of these controversies include improvements in molecular characterization of these diseases and technological advances in surgery and radiology. The relative speed of these advances has outpaced data from clinical trials, in turn making robust data to inform clinical practice lacking. Indeed, many of the current treatment recommendations for the management of liver malignancies are based primarily on retrospective data. We herein review select CER issues concerning select decision-making topics in the management of liver malignancies.


Assuntos
Carcinoma Hepatocelular/terapia , Pesquisa Comparativa da Efetividade/métodos , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Terapia Neoadjuvante , Resultado do Tratamento
19.
AJR Am J Roentgenol ; 205(2): 448-55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26204299

RESUMO

OBJECTIVE: The objective of our study was to compare quantitative maximum breast mass stiffness on shear-wave elastography (SWE) with histopathologic outcome. SUBJECTS AND METHODS: From September 2008 through September 2010, at 16 centers in the United States and Europe, 1647 women with a sonographically visible breast mass consented to undergo quantitative SWE in this prospective protocol; 1562 masses in 1562 women had an acceptable reference standard. The quantitative maximum stiffness (termed "Emax") on three acquisitions was recorded for each mass with the range set from 0 (very soft) to 180 kPa (very stiff). The median Emax and interquartile ranges (IQRs) were determined as a function of histopathologic diagnosis and were compared using the Mann-Whitney U test. We considered the impact of mass size on maximum stiffness by performing the same comparisons for masses 9 mm or smaller and those larger than 9 mm in diameter. RESULTS: The median patient age was 50 years (mean, 51.8 years; SD, 14.5 years; range, 21-94 years), and the median lesion diameter was 12 mm (mean, 14 mm; SD, 7.9 mm; range, 1-53 mm). The median Emax of the 1562 masses (32.1% malignant) was 71 kPa (mean, 90 kPa; SD, 65 kPa; IQR, 31-170 kPa). Of 502 malignancies, 23 (4.6%) ductal carcinoma in situ (DCIS) masses had a median Emax of 126 kPa (IQR, 71-180 kPa) and were less stiff than 468 invasive carcinomas (median Emax, 180 kPa [IQR, 138-180 kPa]; p = 0.002). Benign lesions were much softer than malignancies (median Emax, 43 kPa [IQR, 24-83 kPa] vs 180 kPa [IQR, 129-180 kPa]; p < 0.0001). Usual benign lesions were soft, including 62 cases of fibrocystic change (median Emax, 32 kPa; IQR, 24-94 kPa), 51 cases of fibrosis (median Emax, 36 kPa; IQR, 22-102 kPa), and 301 fibroadenomas (median Emax, 45 kPa; IQR, 30-79 kPa). Eight lipomas (median Emax, 14 kPa; IQR, 8-15 kPa), 154 cysts (median Emax, 29 kPa; IQR, 10-58 kPa), and seven lymph nodes (median Emax, 17 kPa; IQR, 9-40 kPa) were softer than usual benign lesions (p < 0.0001 for lipomas and cysts; p = 0.007 for lymph nodes). Risk lesions were slightly stiffer than usual benign lesions (p = 0.002) but tended to be softer than DCIS (p = 0.14). Fat necrosis and abscesses were relatively stiff. Conclusions were similar for both small and large masses. CONCLUSION: Despite overlap in Emax values, maximum stiffness measured by SWE is a highly effective predictor of the histopathologic severity of sonographically depicted breast masses.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Ultrassonografia Mamária , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Europa (Continente) , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Necrose , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Estados Unidos
20.
Radiographics ; 35(5): 1419-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26273994

RESUMO

Ultrasonography (US) is often the initial imaging modality employed in the evaluation of renal diseases. Despite improvements in B-mode and Doppler imaging, US still faces limitations in the assessment of focal renal masses and complex cysts as well as the microcirculation. The applications of contrast-enhanced US (CEUS) in the kidneys have dramatically increased to overcome these shortcomings with guidelines underlining their importance. This article describes microbubble contrast agents and their role in renal imaging. Microbubble contrast agents consist of a low solubility complex gas surrounded by a phospholipid shell. Microbubbles are extremely safe and well-tolerated pure intravascular agents that can be used in renal failure and obstruction, where computed tomographic (CT) and magnetic resonance (MR) imaging contrast agents may have deleterious effects. Their intravascular distribution allows for quantitative perfusion analysis of the microcirculation, diagnosis of vascular problems, and qualitative assessment of tumor vascularity and enhancement patterns. Low acoustic power real-time prolonged imaging can be performed without exposure to ionizing radiation and at lower cost than CT or MR imaging. CEUS can accurately distinguish pseudotumors from true tumors. CEUS has been shown to be more accurate than unenhanced US and rivals contrast material-enhanced CT in the diagnosis of malignancy in complex cystic renal lesions and can upstage the Bosniak category. CEUS can demonstrate specific enhancement patterns allowing the differentiation of benign and malignant solid tumors as well as focal inflammatory lesions. In conclusion, CEUS is useful in the characterization of indeterminate renal masses and cysts.


Assuntos
Meios de Contraste , Nefropatias/diagnóstico por imagem , Transplante de Rim , Rim/diagnóstico por imagem , Microbolhas , Sistemas Computacionais , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Humanos , Rim/irrigação sanguínea , Doenças Renais Císticas/diagnóstico por imagem , Microbolhas/efeitos adversos , Doenças Renais Policísticas/diagnóstico por imagem , Ultrassonografia
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