RESUMO
To evaluate the benefit of adding CT imaging to the simulation process of clip-based proton therapy of ocular melanomas. For thirty ocular melanoma cases, the clip position in the eye model was determined based on orthogonal radiographs as well as on a CT image set. The geometrical shift of the clips between the standard simulation process and standard simulation process with addition of CT imaging (CT-guided) was determined. The dosimetric impact was evaluated by developing treatment plans based on both the standard-process model and the CT-guided model. In 40% of the studied cases, the difference in clip position between eye models created with and without CT was less than 0.5 mm. This difference was more than 1 mm in 17% of cases. The dosimetric impact of shifts below 1 mm was low because these shifts did not exceed the planning margins. For the four cases with a shift of more than 1 mm a reduction in target coverage (ΔV99%) of -3% to -6% was observed. Changes in macula and optic-disc mean dose of up to 16% and 35% of the prescribed dose were seen when these structures abutted the target. Adding CT imaging to the simulation process is beneficial in select cases where discrepancies between the eye model and ophthalmology measurements occur or where a critical structure is located close to the target and improved localization accuracy is wanted. For the majority of patients, addition of CT imaging does not result in quantifiable changes in dosimetry. Nevertheless, CT imaging is a valuable tool in the quality control of the modeling and treatment-planning process of clip-based eye treatments.
Assuntos
Neoplasias Oculares/diagnóstico por imagem , Neoplasias Oculares/radioterapia , Melanoma/diagnóstico por imagem , Melanoma/radioterapia , Terapia com Prótons/métodos , Radioterapia Guiada por Imagem/métodos , Tomografia Computadorizada por Raios X , Humanos , Terapia com Prótons/instrumentação , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem/instrumentaçãoRESUMO
Heterozygous GATA2 mutations underlie an array of complex hematopoietic and lymphatic diseases. Analysis of the literature reporting three recurrent GATA2 germline (g) mutations (gT354M, gR396Q and gR398W) revealed different phenotype tendencies. Although all three mutants differentially predispose to myeloid malignancies, there was no difference in leukemia-free survival for GATA2 patients. Despite intense interest, the molecular pathogenesis of GATA2 mutation is poorly understood. We functionally characterized a GATA2 mutant allelic series representing major disease phenotypes caused by germline and somatic (s) mutations in zinc finger 2 (ZF2). All GATA2 mutants, except for sL359V, displayed reduced DNA-binding affinity and transactivation compared with wild type (WT), which could be attributed to mutations of arginines critical for DNA binding or amino acids required for ZF2 domain structural integrity. Two GATA2 mutants (gT354M and gC373R) bound the key hematopoietic differentiation factor PU.1 more strongly than WT potentially perturbing differentiation via sequestration of PU.1. Unlike WT, all mutants failed to suppress colony formation and some mutants skewed cell fate to granulocytes, consistent with the monocytopenia phenotype seen in GATA2-related immunodeficiency disorders. These findings implicate perturbations of GATA2 function shaping the course of development of myeloid malignancy subtypes and strengthen complete or nearly complete haploinsufficiency for predisposition to lymphedema.
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Diferenciação Celular/genética , Fator de Transcrição GATA2/genética , Sistema Hematopoético/patologia , Mutação/genética , Transcrição Gênica/genética , Animais , Células COS , Chlorocebus aethiops , Feminino , Predisposição Genética para Doença/genética , Genótipo , Células HEK293 , Haploinsuficiência/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , FenótipoRESUMO
Tyrosine kinase inhibitor (TKI) therapy results in excellent responses in the majority of patients with chronic myeloid leukaemia. First-line imatinib treatment, with selective switching to nilotinib when patients fail to meet specific molecular targets or for imatinib intolerance, results in excellent overall molecular responses and survival. However, this strategy is less effective in cases of primary imatinib resistance; moreover, 25% of patients develop secondary resistance such that 20-35% of patients initially treated with imatinib will eventually experience treatment failure. Early identification of these patients is of high clinical relevance. Since the drug efflux transporter ABCB1 has previously been implicated in TKI resistance, we determined if early increases in ABCB1 mRNA expression (fold change from diagnosis to day 22 of imatinib therapy) predict for patient response. Indeed, patients exhibiting a high fold rise (⩾2.2, n=79) were significantly less likely to achieve early molecular response (BCR-ABL1IS ⩽10% at 3 months; P=0.001), major molecular response (P<0.0001) and MR4.5 (P<0.0001). Additionally, patients demonstrated increased levels of ABCB1 mRNA before the development of mutations and/or progression to blast crisis. Patients with high fold rise in ABCB1 mRNA were also less likely to achieve major molecular response when switched to nilotinib therapy (49% vs 82% of patients with low fold rise). We conclude that early evaluation of the fold change in ABCB1 mRNA expression may identify patients likely to be resistant to first- and second-generation TKIs and who may be candidates for alternative therapy.
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Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/análise , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Células Cultivadas , Resistencia a Medicamentos Antineoplásicos , Expressão Gênica , Humanos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/análiseRESUMO
BACKGROUND: Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. AIM: To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. METHODS: Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). RESULTS: All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29-12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. CONCLUSIONS: HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.
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Fígado Gorduroso/etiologia , Infecções por HIV/complicações , Cirrose Hepática/etiologia , Adulto , Idoso , Povo Asiático , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico por imagem , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico por imagem , Hong Kong/epidemiologia , Humanos , Queratina-18/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/etiologia , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Pretreatment prediction of patients with nasopharyngeal carcinoma who will fail conventional treatment would potentially allow these patients to undergo more intensive treatment or closer posttreatment monitoring. The aim of the study was to determine the ability of pretreatment DWI to predict local failure in patients with nasopharyngeal carcinoma based on long-term clinical outcome. MATERIALS AND METHODS: One hundred fifty-eight patients with pretreatment DWI underwent analysis of the primary tumor to obtain the ADC mean, ADC skewness, ADC kurtosis, volume, and T-stage. Univariate and multivariate analyses using logistic regression were performed to compare the ADC parameters, volume, T-stage, and patient age in primary tumors with local failure and those with local control, by using a minimum of 5-year follow-up to confirm local control. RESULTS: Local control was achieved in 131/158 (83%) patients (range, 60.3-117.7 months) and local failure occurred in 27/158 (17%) patients (range, 5.2-79.8 months). Compared with tumors with local control, those with local failure showed a significantly lower ADC skewness (ADC values with the greatest frequencies were shifted away from the lower ADC range) (P = .006) and lower ADC kurtosis (curve peak broader) (P = .024). The ADC skewness remained significant on multivariate analysis (P = .044). There was a trend toward higher tumor volumes in local failure, but the volume, together with T-stage and ADC mean, were not significantly different between the 2 groups. CONCLUSIONS: Pretreatment DWI of primary tumors found that the skewness of the ADC distribution curve was a predictor of local failure in patients with nasopharyngeal carcinoma, based on long-term clinical outcome.
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Carcinoma/diagnóstico por imagem , Carcinoma/cirurgia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/cirurgia , Adulto , Fatores Etários , Idoso , Determinação de Ponto Final , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Valor Preditivo dos Testes , Falha de Tratamento , Resultado do TratamentoRESUMO
Early molecular response (EMR, BCR-ABL1 (IS)⩽10% at 3 months) is a strong predictor of outcome in imatinib-treated chronic phase chronic myeloid leukemia (CP-CML) patients, but for patients who transform early, 3 months may be too late for effective therapeutic intervention. Here, we employed multiplex cytokine profiling of plasma samples to test newly diagnosed CP-CML patients who subsequently received imatinib treatment. A wide range of pro-inflammatory and angiogenesis-promoting cytokines, chemokines and growth factors were elevated in the plasma of CML patients compared with that of healthy donors. Most of these normalized after tyrosine kinase inhibitor treatment while others remained high in remission samples. Importantly, we identified TGF-α and IL-6 as novel biomarkers with high diagnostic plasma levels strongly predictive of subsequent failure to achieve EMR and deep molecular response, as well as transformation to blast crisis and event-free survival. Interestingly, high TGF-α alone can also delineate a poor response group raising the possibility of a pathogenic role. This suggests that the incorporation of these simple measurements to the diagnostic work-up of CP-CML patients may enable therapy intensity to be individualized early according to the cytokine-risk profile of the patient.
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Interleucina-6/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Indução de Remissão , Fator de Crescimento Transformador alfa/sangue , Crise Blástica , Citocinas/análise , Citocinas/sangue , Intervalo Livre de Doença , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Ativação Linfocitária , Medicina de Precisão , Prognóstico , Fatores de TempoAssuntos
Proteínas de Fusão bcr-abl/genética , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases/genética , Pirimidinas/uso terapêutico , Tiazóis/uso terapêutico , Dasatinibe , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RecidivaRESUMO
PURPOSE: The purpose of this investigation is to determine if a single set of beam data, described by a minimal set of equations and fitting variables, can be used to commission different installations of a proton double-scattering system in a commercial pencil-beam dose calculation algorithm. METHODS: The beam model parameters required to commission the pencil-beam dose calculation algorithm (virtual and effective SAD, effective source size, and pristine-peak energy spread) are determined for a commercial double-scattering system. These parameters are measured in a first room and parameterized as function of proton energy and nozzle settings by fitting four analytical equations to the measured data. The combination of these equations and fitting values constitutes the golden beam data (GBD). To determine the variation in dose delivery between installations, the same dosimetric properties are measured in two additional rooms at the same facility, as well as in a single room at another facility. The difference between the room-specific measurements and the GBD is evaluated against tolerances that guarantee the 3D dose distribution in each of the rooms matches the GBD-based dose distribution within clinically reasonable limits. The pencil-beam treatment-planning algorithm is commissioned with the GBD. The three-dimensional dose distribution in water is evaluated in the four treatment rooms and compared to the treatment-planning calculated dose distribution. RESULTS: The virtual and effective SAD measurements fall between 226 and 257 cm. The effective source size varies between 2.4 and 6.2 cm for the large-field options, and 1.0 and 2.0 cm for the small-field options. The pristine-peak energy spread decreases from 1.05% at the lowest range to 0.6% at the highest. The virtual SAD as well as the effective source size can be accurately described by a linear relationship as function of the inverse of the residual energy. An additional linear correction term as function of RM-step thickness is required for accurate parameterization of the effective SAD. The GBD energy spread is given by a linear function of the exponential of the beam energy. Except for a few outliers, the measured parameters match the GBD within the specified tolerances in all of the four rooms investigated. For a SOBP field with a range of 15 g/cm2 and an air gap of 25 cm, the maximum difference in the 80%-20% lateral penumbra between the GBD-commissioned treatment-planning system and measurements in any of the four rooms is 0.5 mm. CONCLUSIONS: The beam model parameters of the double-scattering system can be parameterized with a limited set of equations and parameters. This GBD closely matches the measured dosimetric properties in four different rooms.
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Algoritmos , Terapia com Prótons/instrumentação , Radiometria/métodos , Dosagem Radioterapêutica , Modelos Lineares , Planejamento da Radioterapia Assistida por Computador/métodos , Espalhamento de Radiação , ÁguaRESUMO
We present three cases of the rare hepatosplenic T-cell lymphoma (HSTCL); two patients suffering from Crohn disease who developed HSTCL on azathioprine without exposure to biologicals, and a third patient who had psoriasis treated using etanercept, cyclosporine and methotrexate. The evidence for an association between HSTCL and immunosuppressive drugs and biologicals is reviewed. We argue for improved pharmacovigilance processes to help determine the benefit to risk ratios for the use of these and other new agents.
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Produtos Biológicos/efeitos adversos , Imunossupressores/efeitos adversos , Neoplasias Hepáticas/diagnóstico , Linfoma de Células T/diagnóstico , Neoplasias Esplênicas/diagnóstico , Adulto , Humanos , Neoplasias Hepáticas/induzido quimicamente , Linfoma de Células T/induzido quimicamente , Masculino , Fatores de Risco , Neoplasias Esplênicas/induzido quimicamenteRESUMO
PURPOSE: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systems and evaluated in the context of the specific clinical requirements of ocular treatments. METHODS: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm(2); the modulation width can be varied in steps of 0.3 g/cm(2) or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). RESULTS: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm(2), larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ± 2%. Neutron dose is found to be 146 ± 102 µSv/Gy at the contralateral eye and 19 ± 13 µSv/Gy at the chest. CONCLUSIONS: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.
Assuntos
Neoplasias Oculares/radioterapia , Terapia com Prótons/métodos , Humanos , Nêutrons/uso terapêutico , Imagens de Fantasmas , Radiometria , Dosagem RadioterapêuticaRESUMO
BACKGROUND: BCR-ABL1 mutation analysis is recommended for chronic myeloid leukaemia patients. However, mutations may become undetectable after changing therapy, and it is unknown whether they have been eradicated. METHODS: We examined longitudinal data of patients with imatinib-resistant mutations, which became undetectable by Sanger sequencing to determine whether mutations could reappear, and the related circumstances. RESULTS: Identical imatinib- and nilotinib-resistant mutations reappeared following further therapy changes in five patients, and was associated with subsequent nilotinib resistance in four. CONCLUSION: The data suggest that some BCR-ABL1 mutations may persist at undetectable levels for many years after changing therapy, and can be reselected and confer resistance to subsequent inhibitors.
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Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Adulto , Idoso , Benzamidas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacologia , Pirimidinas/farmacologia , Estudos RetrospectivosRESUMO
PURPOSE: This study investigated the volumetric relationship of white matter lesion (WML) and contrast-enhanced lesion (CEL) in delayed radiation brain injury (RBI) during the course of evolution. MATERIALS AND METHODS: MRI results in 45 patients with RBI after receiving radiation for nasopharyngeal carcinoma were analyzed. In total there were 75 lobes with RBI and 114 MRI examinations in this study. WML and CEL lesion volumes were measured. The lesion volume change of less than 5% or 0.25 cm(3) was regarded as being static. RESULTS: The average WML volume was 16.33 cm(3) (ranging 0.11 cm(3) to 102.83 cm(3)), and the average CEL volume was 3.15 cm(3) (ranging 0.03 cm(3) to 27.85 cm(3)). WML was larger than CEL in 164 measurements, and CEL was larger than WML in 10 measurements. In 64.3% follow-ups WML and CEL evolved in the same pattern; and in most follow-ups (93.8%) WML and CEL did not evolve in the opposite directions. A larger WML volume tended to have a larger CEL volume though this relationship was not linear. CONCLUSION: Evolution of WML and CEL tended to follow the same pattern. WML tended to be larger than CEL, and larger WML tended to be associated with larger CEL.
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Encéfalo/efeitos da radiação , Leucoencefalopatias/patologia , Lesões por Radiação/patologia , Adulto , Idoso , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: T2-weighted MRI shows potential in early posttreatment assessment of the primary tumor. Residual masses composed entirely of low T2-signal scar tissue suggest local control and those ≥1 cm of similar signal to untreated tumor suggest local failure. The purpose of this study was to investigate the diagnostic accuracy of T2-weighted MR imaging early after chemoradiotherapy for identifying primary tumor treatment failure in squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: At 6 weeks after treatment, T2-weighted MR images of 37 primary tumors in 37 patients were assessed. Residual masses were divided into 3 patterns: pattern 1 = scar tissue only (flat-edged/retracted mass of low T2 signal intensity); pattern 2 = mass without features described in pattern 1 or 3; and pattern 3 = any pattern that included an expansile mass ≥1 cm of intermediate T2 signal intensity (similar grade of signal intensity to the untreated tumor). T2 patterns were analyzed for local outcome (Fisher exact test) and time to local failure (univariate and multivariate analysis of T2 pattern, age, T stage, and tumor size by use of the Cox regression model). RESULTS: Residual masses after treatment were present in 34 (92%) of 37 patients. Local failures occurred in residual masses with pattern 1 in 0 (0%) of 14 patients; pattern 2 in 6 (55%) of 11 patients; and pattern 3 in 9 (100%) of 9 patients. Significant associations were found between local control and pattern 1 (P = <.0001; sensitivity, 74%; specificity, 100%; PPV, 100%; NPV, 75%; accuracy, 85%), and between local failure and pattern 3 (P = <.0001; sensitivity, 60%; specificity, 100%; PPV, 100%; NPV, 76%; accuracy, 82%). Pattern 2 showed no significant associations with local outcome. Univariate analysis of time to local failure showed that the T2 pattern was significant (P < .0001) and remained significant on multivariate analysis. CONCLUSIONS: T2-weighted MR imaging is a potential tool for early posttreatment assessment of primary HNSCC treatment response. Awareness of correlation of the T2 pattern of any residual mass with treatment outcome at the primary site may contribute to patient treatment.
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Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Imagem de Difusão por Ressonância Magnética/normas , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Falha de TratamentoRESUMO
BACKGROUND: The diagnosis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non-invasive assessments are urgently needed. AIM: To evaluate cell apoptotic marker cytokeratin-18 M30 and total cell death markers cytokeratin-18 M65/M65ED for the assessment and monitoring of NAFLD. METHODS: A cohort of 147 patients with biopsy-proven NAFLD and 73 controls were enrolled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme-linked immunosorbent assay. RESULTS: M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non-NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver-operating characteristics curve above 0.8 in predicting disease progression. At cut-off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression. CONCLUSIONS: Cytokeratin-18 M30 and M65/M65ED have moderate accuracy in detecting non-alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.
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Biomarcadores/sangue , Fígado Gorduroso/sangue , Queratina-18/sangue , Fragmentos de Peptídeos/sangue , Adulto , Apoptose , Estudos de Casos e Controles , Morte Celular , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica , Valor Preditivo dos TestesRESUMO
PURPOSE: To commission a proton-therapy system for the treatment of uveal melanoma and age-related macular degeneration. METHODS: Proton therapy system is the proto-type of a commercial product developed by Ion Beam Applications. Proton beam is brought into the treatment room at 105 MeV through a fixed beam line. A single-scattering system with absorber/scattering foils spreads the beam into a Gaussian profile. A library of 10 range-modulator wheels and 16 range-modulator blocks generate spread-out Bragg peaks of various range and modulation width. Source-to-axis distance of the system is 169 cm. Two orthogonal digital x-ray panels are used for alignment. EyePlan software is used both for both treatment planning and in-room alignment. RESULTS: Range can be varied continuously between 0.5 and 3.4 g/cm2 . Range accuracy is measured to be better than 0.05 g/cm2 . Modulation width can be varied in steps of =0.3 g/cm2 with an accuracy of 0.05 g/cm2 or 2%. Maximum aperture diameter is 2.5 cm and maximum dose rate >32 Gy/min. Strong dependence of output on range (7%/mm) and dose rate (0.2%/(Gy/min)) is found. Distal and lateral fall-off (80%-20%) are =0.23 and =0.18 g/cm2 and do not depend much on range or depth. When reducing the aperture diameter to 6 mm no significant change is observed in shape of depth-dose curve or absolute dose (<2.5%). Measurements show a significant portion of the dose at shallow depth (=0.7 g/cm2 ) is delivered by protons scattering off of snout elements. Simple collimation could reduce this effect. CONCLUSION: The dosimetric and positioning properties of the IBA ocular proton system are adequate to treat ocular lesions with acceptable clinical margins. Suggested improvements include limiting the output-dependence on range and reducing snout scatter.
RESUMO
AIMS: Central venous catheters (CVC) are integral to modern haematology practice; however, they are associated with a range of complications. This prospective study aimed to determine the rate of CVC-related complications and risk factors in haematology patients, who are vulnerable because of their underlying pathology and treatments. METHODS: All inpatients that had a non-tunnelled CVC inserted in a 14-month period in the haematology ward at St Vincent's Hospital were enrolled. Complications (immediate and late), demographics, type of device, insertion technique and duration of dwell, were examined using multivariate analysis. RESULTS: One hundred and seventy-four CVC in 84 patients were recorded, representing 3016 catheter-days. At least one complication was found in 43 (24.7%) patients. Immediate complications occurred in 13 (7.5%) insertions, with a higher rate in those inserted after ≥2 attempts compared with one (P = 0.02). Catheter-related bloodstream infection occurred at a rate of 7.6 per 1000 catheter-days, with acute lymphoblastic leukaemia associated with a higher rate (P = 0.02), and subclavian vein CVC had a lower rate compared with other locations (P < 0.01). Thrombosis was found in seven (4.0%) patients, with subclavian CVC carrying an increased risk (P = 0.02). CONCLUSIONS: This prospective observational study found almost a quarter of haematology patients experience a CVC-related complication. An association was found with a number of attempts at insertion and immediate complications; other risk factors included anatomical location, underlying disease and duration of catheterisation. The relatively high complication rate, compared with reports of non-haematology patients, highlights the need to improve CVC management, a vital part of care for this population.
Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Adulto , Idoso , Infecções Relacionadas a Cateter/diagnóstico , Cateterismo Venoso Central/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
AIM: To devise a method to convert the time-intensity curves (TICs) of head and neck dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data into a pixel-by-pixel colour-coded map for identifying normal tissues and tumours. MATERIALS AND METHODS: Twenty-three patients with head and neck squamous cell carcinoma (HNSCC) underwent DCE-MRI. TIC patterns of primary tumours, metastatic nodes, and normal tissues were assessed and a program was devised to convert the patterns into a classified colour-coded map. The enhancement patterns of tumours and normal tissue structures were evaluated and categorized into nine grades (0-8) based on the predominance of coloured pixels on maps. RESULTS: Five identified TIC patterns were converted into a colour-coded map consisting of red (maximum enhancement), brown (continuous slow rise-up), yellow (rapid wash-in and wash-out), green (rapid wash-in and plateau), and blue (rapid wash-in and rise-up). The colour-coded map distinguished all 21 primary tumours and 15 metastatic nodes from normal structures. Primary tumours and metastatic nodes were colour coded as predominantly yellow (grades 1-2) in 17/21 and 6/15, green (grades 3-5) in 3/21 and 5/15, and blue (grades 6-7) in 1/21 and 4/15, respectively. Vessels were coded red in 46/46 (grade 0) and muscles were coded brown in 23/23 (grade 8). Salivary glands, thyroid glands, and palatine tonsils were coded into predominantly yellow (grade 1) in 46/46 and 10/10 and 18/22, respectively. CONCLUSION: DCE-MRI derived five-colour-coded mapping provides an objective easy-to-interpret method to assess the dynamic enhancement pattern of head and neck cancers.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Cor , Meios de Contraste , Gadolínio DTPA , HumanosRESUMO
The utility of diffusion-weighted imaging (DWI) in the detection of squamous cell carcinoma (SCC) of the tonsils has not been previously investigated. This preliminary study compared DWI of apparent SCC tonsillar tumours with normal tonsils. DWI of the tonsils was performed in 10 patients with newly diagnosed tonsil SCC that was evident on conventional MRI and in 17 patients undergoing cranial MRI for other indications. Regions of interest (ROI) were drawn around each identifiable tonsil on the apparent diffusion coefficient (ADC) map and the mean ADC value for each tonsil was calculated. ADC values for normal and SCC tonsils were compared using the Mann-Whitney U-test. The median ADC and range (x10(-3) mm(2) s(-1)) were found to be 0.814 and 0.548-1.312, respectively, for normal tonsils compared with 0.933 and 0.789-1.175, respectively, for SCC tonsils. ADC values were significantly higher for SCC tonsils than for normal tonsils (p = 0.009). No SCC tonsil had an ADC less than 0.82 x 10(-3) mm(2) s(-1) compared with 58% of normal tonsils. We conclude that there is a difference in the ADC between normal tonsils and SCC tonsils where the cancer is apparent on conventional MRI. These results are promising, although further studies are now required to determine whether DWI can be used to identify or exclude smaller foci of SCC within tonsils where the cancer is not evident on conventional MRI.