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1.
Am J Dermatopathol ; 44(4): 302-305, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34816804

RESUMO

ABSTRACT: Inflammatory myofibroblastic tumors are rare soft tissue neoplasms with an uncertain biological behavior, derived from fibroblastic and myofibroblastic cells. In rare cases, a peculiar epithelioid phenotypic variant of this tumor is encountered, named epithelioid inflammatory myofibroblastic sarcoma (EIMS). EIMS has overlapping features with inflammatory myofibroblastic tumor but has been correlated with a more aggressive clinical course, a characteristic nuclear membrane or perinuclear anaplastic lymphoma kinase (ALK) immunostaining pattern and a very specific RANBP2-ALK fusion. To date, EIMS has been reported almost exclusively in the abdominal and pelvic cavity, with the exception of some intrathoracic cases. Herein, we present the first case of primary cutaneous EIMS, confirmed by molecular analysis showing the diagnostic RANBP2-ALK fusion.


Assuntos
Sarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Quinase do Linfoma Anaplásico/genética , Diagnóstico Diferencial , Feminino , Humanos , Chaperonas Moleculares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Coxa da Perna
2.
Front Immunol ; 12: 736498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557196

RESUMO

Immune escape is an early phenomenon in cancer development/progression. Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. This study investigated the clinical relevance of IDO1 expression by immune cells in the lymph nodes and blood and of the serum kynurenine/tryptophan (Kyn/Trp) ratio in 65 systemic treatment naïve stage I-III melanoma patients. Blood samples were collected within the first year of diagnosis. Patients had a median follow-up of 61 months. High basal IDO1 expression in peripheral monocytes and low IFNγ-induced IDO1 upregulation correlated with worse outcome independent from disease stage. Interestingly studied factors were not interrelated. During follow-up, the risk of relapse was 9% (2/22) in the subgroup with high IFNγ-induced IDO1 upregulation in monocytes. In contrast, if IDO1 upregulation was low, relapse occurred in 30% (3/10) of patients with low basal IDO1 expression in monocytes and in 61.5% (8/13) in the subgroup with high basal IDO1 expression in monocytes (Log-Rank test, p=0.008). This study reveals some immune features in the blood of early stage melanoma that may be of relevance for disease outcome. These may offer a target for sub-stratification and early intervention.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Interferon gama/farmacologia , Cinurenina/sangue , Melanoma/sangue , Monócitos/efeitos dos fármacos , Neoplasias Cutâneas/sangue , Triptofano/sangue , Adulto , Células Cultivadas , Indução Enzimática , Feminino , Humanos , Masculino , Melanoma/enzimologia , Melanoma/imunologia , Melanoma/terapia , Pessoa de Meia-Idade , Monócitos/enzimologia , Monócitos/imunologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Fatores de Tempo , Resultado do Tratamento , Evasão Tumoral
3.
Eur J Radiol ; 107: 143-148, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30292259

RESUMO

OBJECTIVE: To evaluate a dynamic contrast-enhanced CT-protocol and compare this method with standard of care monophasic portovenous CT for detection of colorectal liver metastases. MATERIALS AND METHODS: A dynamic contrast-enhanced CT protocol was developed to detect liver metastasis in patients suffering from colorectal cancer, in clinical practice. The study was approved by the Hospital Ethics Committee. Written informed consent was obtained from all patients. 135 patients were included in this prospective study. All patients were naive to treatment. A dynamic contrast-enhanced CT was performed, followed by routine monophasic portovenous CT of thorax-abdomen-pelvis. 42 of these patients presented with liver metastasis. The number and lesion conspicuity of detected liver metastasis on dynamic contrast-enhanced CT using perfusion maps, was compared to monophasic CT. RESULTS: 135 patients were included, of which 42 presented with metastases to the liver. Dynamic contrast-enhanced CT outperformed portovenous CT for detection as well as conspicuity of colorectal liver metastasis, at a relatively low dose increment. Wilcoxon Signed Rank test had a p-value of 0.016 and <0.001 respectively for detection and conspicuity of colorectal liver metastasis. CONCLUSION: Dynamic contrast-enhanced CT increases the detection of colorectal liver metastasis, especially for lesions smaller than 15 mm, when compared to monophasic portovenous CT. Dynamic contrast-enhanced CT also has the added advantage of improved lesion conspicuity, which can positively influence reader confidence and clinical workflow.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Meios de Contraste , Humanos , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada Espiral/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
4.
J Am Acad Dermatol ; 78(6): 1164-1170, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29066274

RESUMO

BACKGROUND: Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder, and its pathogenesis and long-term prognosis are unknown. OBJECTIVE: To elucidate the clinical and histopathologic characteristics, pathogenesis, and outcome in patients with SHJCM. METHODS: Retrospective study of 9 patients with SHCJM. To complement initial findings, data collection forms were sent to the referring physicians. RESULTS: All patients had an acute onset of firm nodules. Of the 9 patients, 6 presented initially with waxy papules on the dorsum of the hands; 5 suffered from periorbital edema, and 6 had a febrile prodrome. Histopathologic assessment of the papules revealed dermal mucin deposition, whereas the nodules showed proliferative fasciitis-like features or nonspecific chronic lobular panniculitis. Laboratory studies elicited evidence of active viral infection in 2 patients (human herpes virus 6 and rotavirus). Seven cases had spontaneous resolution within 6 months, and 2 patients with incomplete resolution showed subsequent transition to fibroblastic rheumatism and an autoinflammatory rheumatologic disease, respectively. LIMITATIONS: This was a retrospective study with incomplete data from referring physicians. CONCLUSIONS: Although spontaneous complete regression is expected, patients with SHJCM need long-term follow-up because of the possible development of dematorheumatolgic conditions. The pathogenetic role of microbial agents deserves further investigation.


Assuntos
Mucinoses/patologia , Mucinoses/fisiopatologia , Remissão Espontânea , Dermatopatias Papuloescamosas/patologia , Dermatopatias Papuloescamosas/fisiopatologia , Fatores Etários , Biópsia por Agulha , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Incidência , Lactente , Masculino , Monitorização Fisiológica/métodos , Mucinoses/epidemiologia , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Índice de Gravidade de Doença , Fatores Sexuais , Dermatopatias Papuloescamosas/epidemiologia , Fatores de Tempo
5.
Br J Radiol ; 90(1076): 20170007, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28590780

RESUMO

OBJECTIVE: To examine if intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced MRI (DCE-MRI) can be used as new and supplemental MRI techniques to differentiate hepatocellular adenomas (HCAs) from focal nodular hyperplasias (FNHs) and analyse if diffusion parameter apparent diffusion coefficient (ADC) and IVIM parameter true diffusion coefficient (D) differ in doing so. METHODS: This prospective study included 21 patients (8 HCAs and 13 FNHs) who underwent a specifically designed MRI scanning protocol, including series for analysis of IVIM (four b-values 0, 10, 150 and 800 s mm-2) and DCE-MRI. On a dedicated workstation, identical regions of interest were placed in parametric maps of Ktrans, Ve, D and ADC in each lesion for quantification. Diagnostic accuracy was assessed using receiver operating characteristics analysis. Time-intensity curves (TICs) were classified in different types. RESULTS: HCAs had significantly lower values for Ktrans (mean 1.45 vs 2.68 min-1; p = 0.029) and D (mean 1.02 × 10-3 vs 1.22 × 10-3 mm2 s-1; p = 0.033). Both parameters showed good diagnostic accuracy of 76%. TIC analysis could not differentiate between HCAs and FNHs. CONCLUSION: In this exploratory study, Ktrans and D were able to differentiate HCAs from FNHs in most cases, whereas Ve, ADC and TIC analysis were not. Advances in knowledge: Histological differences between HCAs and FNHs can be quantified on MRI using Ktrans and D.


Assuntos
Adenoma de Células Hepáticas/diagnóstico por imagem , Meios de Contraste , Hiperplasia Nodular Focal do Fígado/diagnóstico por imagem , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Diagnóstico Diferencial , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Movimento (Física) , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
JAMA Dermatol ; 153(2): 154-161, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28030717

RESUMO

IMPORTANCE: Ex vivo dermoscopy (EVD) with derm dotting (DD) improves clinicopathologic correlation and the quality of diagnosis in skin tumors. OBJECTIVE: To compare the diagnostic performance of the standard method of skin biopsy processing with the practice of EVD with DD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study compares the diagnostic performance in 6526 skin biopsy specimens examined from 2008 to 2010 with a standard method of processing with 8584 biopsy specimens examined in 2015 with EVD and DD. Data were analyzed from January 1 to March 31, 2016. A total of 15 110 skin biopsy specimens were included. The biopsy specimens from 2008 to 2010 were processed in a hospital-based general pathology laboratory; the biopsy specimens from 2015 were processed in a private dermatopathology laboratory. Biopsy specimens from both periods were diagnosed by the same dermatopathologist. MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinicopathological characteristics, usefulness of EVD with DD, and turnaround times (TATs). RESULTS: Use of EVD with DD increased the detection of positive section margins in nonmelanoma skin cancer from 8.4% to 12.8%. The most significant increase was seen in Bowen disease, invasive squamous cell carcinoma, and a superficial type of basal cell carcinoma (BCC). With EVD and DD, a specific clinicopathologic diagnosis was made in 27.7% of nevi compared with only 10.3% using the standard method. The incidence of moderately and severely dysplastic nevi increased from 1.0% to 7.2% and from 0.6% to 1.4%, respectively. The detection of ulceration in melanomas with thicker than 1 mm increased from 24.0% to 31.3%. The number of nevi-associated melanomas increased from 15.5% to 33.3%. The number of collision lesions from 0.07% to 1.07%. The TAT for nevi decreased from 2 days to 1 day, for melanomas from 5 days to 2 days, and for BCC from 2 days to 1 day. CONCLUSIONS AND RELEVANCE: Ex vivo dermoscopy and DD with adapted sectioning in a dermatopathology setting allows a more accurate and less time consuming histopathologic diagnosis of skin tumors. These findings suggest that pathologists involved in skin tumor evaluation should be encouraged to learn dermoscopy and replace random transverse cutting with lesion-specific and DD-guided cutting.

7.
JAMA Dermatol ; 152(3): 312-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26746141

RESUMO

IMPORTANCE: Ex vivo dermoscopy (EVD) can be a valuable tool in routine diagnostic dermatopathologic evaluation. OBJECTIVES: To compare in vivo dermoscopy (IVD) and EVD and to provide guidance for routine dermatopathologic evaluations. DESIGN, SETTING, AND PARTICIPANTS: This observational study collected 101 consecutive IVD and EVD images of skin tumors from a private dermatology practice from March 1 to September 30, 2013. Four observers (3 dermatologists and 1 dermatopathologist) blinded to the histopathologic diagnoses independently scored and compared the colors, structures, and vessels of EVD images with those of the corresponding IVD images. Data were analyzed from January 1 to March 31, 2014. MAIN OUTCOMES AND MEASURES: Concordance between the EVD and IVD images and gain or loss of colors, structures, and vessels on EVD relative to IVD images. RESULTS: The final analysis included 404 observations of 101 images. The EVD image was generally similar to the corresponding IVD image but clearly darker, with new areas of blue in 130 of 404 observations (32.2%) and white in 100 of 404 observations (24.8%) and loss of red in 283 of 404 observations (70.0%). Most structures were well preserved. New structureless areas were found in 78 of 404 observations of EVD images (19.3%), and new crystalline structures were detected in 68 of 404 observations of EVD images (16.8%). On EVD images, squames and crusts were lost in 56 of 404 observations (13.9%) and 43 of 404 observations (10.6%), respectively. Blood vessels were lost in 142 of 404 observations of EVD images (35.1%). CONCLUSIONS AND RELEVANCE: The EVD image is an important new tool in dermatopathology and may give direction to targeted tissue processing and examination of skin tumors.


Assuntos
Dermoscopia/métodos , Neoplasias Cutâneas/patologia , Biópsia , Carcinoma Basocelular/patologia , Diagnóstico Diferencial , Humanos , Técnicas In Vitro , Melanoma/patologia , Nevo Pigmentado/patologia , Variações Dependentes do Observador , Pele/patologia , Estatística como Assunto
8.
Radiology ; 269(2): 469-74, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23847252

RESUMO

PURPOSE: To prospectively evaluate dose reduction and image quality characteristics of abdominal computed tomographic (CT) scans reconstructed with model-based iterative reconstruction (MBIR) compared with adaptive statistical iterative reconstruction (ASIR) in oncology patients with colorectal liver metastases. MATERIALS AND METHODS: The study complied with HIPAA guidelines and was approved by the ethics committee of the institutional review board. All patients gave written informed consent. Fifty-one patients with colorectal liver metastases underwent body CT (thorax and abdomen) with a 64-section multidetector unit. With a radiation dose reduction by 2.36 mGy compared to standard of care CT with ASIR 50% (radiation dose, 7.54 mGy), MBIR can provide diagnostically acceptable CT scans without compromising image quality. Two radiologists independently assessed randomized images in a blinded manner. Imaging sets were compared for lesion detection, lesion conspicuity, overall image quality, and signal-to-noise ratio with a paired sample t test. Inter- and intraobserver agreement was assessed with the Cohen κ. RESULTS: The mean volume CT dose index was 5.18 mGy ± 0.76, mean dose-length product 374 mGy · cm ± 63.47, mean effective diameter 29.38 cm ± 3.46, and mean size-specific dose estimate 6.52 mGy ± 0.73. In small liver lesions (<10 mm), detection and conspicuity were significantly higher with MBIR than with ASIR for both right (t = 3.245, P = .004 and t = 2.696, P = .013, respectively) and left (t = 2.390, P = .038 and t = 2.283, P = .046) liver lobes. Subjective image noise (t = 4.506, P < .001), artifacts (t = 3.479, P = .001), and diagnostic confidence (t = 2.643, P = .011) were significantly better with MBIR than with ASIR. CONCLUSION: MBIR performed better than ASIR 50% at providing diagnostically acceptable CT scans without compromising image quality and in the detection of colorectal liver metastases.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Abdominal/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Iohexol/análogos & derivados , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doses de Radiação
11.
Eur J Radiol ; 81(12): 3870-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22944331

RESUMO

PURPOSE: To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prediction and early monitoring of treatment in colorectal liver metastases. MATERIALS AND METHODS: Ten patients were included. Baseline and follow-up DCE-MRI examinations were evaluated by whole tumour and selected ROI placements calculating Kep-values. Selective ROIs, concentric-like and hot spot, were drawn on early arterial phase images. Monitoring of treatment was performed comparing RECIST1.1 criteria with whole tumour and selected ROI placement. To evaluate treatment effect between responders and non-responders, independent samples t-test was used on Kep-values. RESULTS: In each patient largest lesion was evaluated totalling 10 target lesions. At baseline, for whole tumour ROI placements mean Kep-values in responders were significantly higher than mean Kep-values in non-responders (t=7.481, p<0.001). Selective ROI placement comparison of mean Kep-values at baseline and after 6 weeks of treatment (first follow-up measurement) showed significant decrease in responding patients (t=4.706, p=0.003) whereas increase in Kep-values in non-responding patients was not statistically significant. CONCLUSION: This preliminary study shows that baseline Kep for whole tumour ROI is a predictor for treatment outcome. Decrease of Kep using selective ROIs allows early identification of response after 6 weeks of treatment.


Assuntos
Carcinoma/secundário , Carcinoma/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
12.
Eur J Cancer ; 48(13): 2004-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22033321

RESUMO

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), an enzyme with immunosuppressive properties is considered as a factor that impairs the antitumour immune response in melanoma. In this study, we investigated the expression of IDO in sentinel nodes of melanoma patients to determine its prognostic relevance. PATIENTS AND METHODS: One hundred and sixteen melanoma patients were enrolled in this study with a median follow-up time after diagnosis of 71 months. The expression of IDO and forkhead box P3 (Foxp3) in the sentinel lymph nodes was determined by immunohistochemistry and correlated with progression-free survival and overall survival. In 42 patients, regulatory T cells were investigated by flow cytometry. RESULTS: Cox regression survival analysis showed a significant negative effect of IDO expression on progression-free survival (p = 0.015) and overall survival (p = 0.010). High IDO expression was correlated with a significant higher frequency of Foxp3-positive cells in uninvaded lymph nodes (p = 0.016). The presence of IDO expression in the sentinel nodes was not associated with an increased frequency of circulating regulatory T cells (Tregs) but was significantly correlated with an increased mean fluorescence intensity of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) in Tregs (p = 0.019). After CD3CD28 stimulation, peripheral blood mononuclear cells of patients with high IDO expression showed a lower production of interferon-gamma (IFN-γ) (p = 0.025). CONCLUSIONS: This study points to an independent predictive role of IDO on survival, especially in melanoma patients with uninvolved sentinel nodes. Investigating IDO expression in the sentinel nodes of melanoma patients may be a useful marker to pre-identify patients with a less favourable prognosis in stage I and II disease.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Linfonodos/metabolismo , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Antígeno CTLA-4/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Metástase Linfática , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Linfócitos T Reguladores/imunologia
13.
Arthritis Res Ther ; 13(1): R35, 2011 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-21356083

RESUMO

INTRODUCTION: The aims of the present study were to identify histopathological parameters which are linked to local clinical skin disease at two distinct anatomical sites in systemic sclerosis (SSc) patients with skin involvement (limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc)) and to determine the sensitivity of SSc specific histological alterations, focusing on SSc patients without clinical skin involvement (limited SSc (lSSc)). METHODS: Histopathological alterations were systematically scored in skin biopsies of 53 consecutive SSc patients (dorsal forearm and upper inner arm) and 18 controls (upper inner arm). Clinical skin involvement was evaluated using the modified Rodnan skin score. In patients with lcSSc or dcSSc, associations of histopathological parameters with local clinical skin involvement were determined by generalised estimation equation modelling. RESULTS: The hyalinised collagen score, the myofibroblast score, the mean epidermal thickness, the mononuclear cellular infiltration and the frequency of focal exocytosis differed significantly between biopsies with and without local clinical skin involvement. Except for mononuclear cellular infiltration, all of the continuous parameters correlated with the local clinical skin score at the dorsal forearm. Parakeratosis, myofibroblasts and intima proliferation were present in a minority of the SSc biopsies, but not in controls. No differences were found between lSSc and controls. CONCLUSIONS: Several histopathological parameters are linked to local clinical skin disease. SSc-specific histological alterations have a low diagnostic sensitivity.


Assuntos
Esclerodermia Limitada/patologia , Escleroderma Sistêmico/patologia , Pele/patologia , Adulto , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
15.
Eur J Radiol ; 74(3): 529-35, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19375256

RESUMO

PURPOSE: To prospectively evaluate a new imaging sequence (4D THRIVE) for whole liver perfusion in high temporal and spatial resolution. Feasibility of parametric mapping and its potential for characterizing focal liver lesions (FLLs) are investigated. MATERIALS AND METHODS: Fifteen patients suspected for colorectal liver metastases (LMs) were included. Parametric maps were evaluated qualitatively (ring-enhancement and lesion heterogeneity) and compared to three-phased contrast-enhanced MRI. Quantitative analysis was based on average perfusion values of entire FLLs. Reference standard comprised surgery with histopathology or follow-up imaging. Fisher's exact test was used for qualitative and Kruskal-Wallis test for quantitative analysis. RESULTS: In total 29 LMs, 17 hemangiomas and 4 focal nodular hyperplasias were evaluated. FLLs could be differentiated by qualitative assessment of parametric maps respectively three-phased contrast-enhanced MRI (Fisher's p<0.001 for comparisons between LMs and hemangiomas and LMs and FNHs for both ring-enhancement and lesion heterogeneity) rather than by quantitative analysis of parametric maps (Chi-square for Kep=0.33 (p=0.847) and Chi-square for Kel=1.35 (p=0.509)). CONCLUSION: This preliminary study shows potential of 4D THRIVE for whole liver imaging enabling calculation of parametric maps. Qualitative rather than quantitative analysis was accurate for differentiating malignant and benign FLLs.


Assuntos
Algoritmos , Neoplasias Colorretais/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Angiografia por Ressonância Magnética/métodos , Estudos de Viabilidade , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
J Cutan Pathol ; 36(6): 629-36, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19222696

RESUMO

BACKGROUND: RhoC overexpression in tumor cells promotes invasive and metastatic behavior. RhoC expression levels have been correlated with tumor progression and metastasis in multiple human cancers. In melanoma, RhoC is upregulated in highly metastatic tumors. Induced expression in melanoma cell lines resulted in invasion and metastasis, whereas inhibition of RhoC reversed the metastatic phenotype both in vitro and in vivo. METHODS: RhoC mRNA and protein expression in two human melanoma cell lines (DX3aza and MeWo) and pooled primary melanocytes were investigated by means of real-time quantitative polymerase chain reaction and western blotting. RhoC protein expression was evaluated in 123 primary cutaneous melanoma samples by the use of immunohistochemistry and correlated with known prognostic features. RESULTS: RhoC upregulation was observed in the highly metastatic DX3aza cell line, whereas in MeWo, only low expression levels could be detected. RhoC expression in primary cutaneous melanoma was strongly associated with thicker and ulcerated tumors. RhoC expression was associated with the presence of lymphatic metastases at the time of diagnosis and shorter disease-free and overall survival rates, without being an independent predictor. CONCLUSION: These results further support a role for RhoC in growth and metastasis of melanoma.


Assuntos
Melanoma/metabolismo , Melanoma/patologia , Invasividade Neoplásica/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteínas rho de Ligação ao GTP/metabolismo , Western Blotting , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/genética , Proteínas rho de Ligação ao GTP/genética , Proteína de Ligação a GTP rhoC
17.
Eur J Radiol ; 69(1): 131-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17950553

RESUMO

PURPOSE: To assess the added value of true diffusion (D), perfusion factor (f) and apparent diffusion coefficient at low b-values (ADC(low)) for differentiation between liver metastases and hemangiomas based on respiratory-triggered high-resolution Black-Blood Single-Shot SpinEcho Echo Planar Imaging (BB SS SE-EPI). MATERIALS AND METHODS: Twenty-five patients suspected for malignant colorectal liver lesions were included in this study. A total of 106 lesions were examined. Different b-value images were compared for lesion conspicuity, image quality and artifacts using rank order statistic (RIDIT) and Student's t-test. D, f, and ADC(low) values were calculated. Pearson correlation coefficient is used for comparison of interobserver variability. RESULTS: Best lesion conspicuity (p<0.05) was achieved with BB SS SE-EPI (b=0 and 10s/mm(2)); best image quality (p<0.05) with b=10s/mm(2). Image artifacts were lowest (p<0.05) with b=0s/mm(2). Over the whole sample, D in metastases (D(met)) was significantly (p<0.05) lower than D in hemangiomas (D(hem)); f and ADC(low) of metastases (f(met), respectively, ADC(lowmet)) were significantly (p<0.05) higher than f and ADC(low) of hemangiomas (f(hem), respectively, ADC(lowhem)). All Pearson correlations were statistically significant at a 0.01 level. CONCLUSIONS: This preliminary study shows the potential of BB SS SE-EPI as a useful technique to aid in differentiating between liver metastasis and hemangioma. The calculation of D, f and ADC(low) provides useful additional information for differentiating metastases from hemangiomas.


Assuntos
Neoplasias Colorretais/patologia , Imagem Ecoplanar/métodos , Hemangioma/patologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Eur J Radiol ; 72(3): 432-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18849130

RESUMO

PURPOSE: To compare lesion conspicuity and image quality between single-shot spin echo echo planar imaging (SS SE-EPI) before, immediately and 5min after intravenous (IV) injection of superparamagnetic iron oxide (SPIO) for detecting and characterizing focal liver lesions (FLLs). MATERIALS AND METHODS: Twenty-five patients suspected for colorectal liver metastases were prospectively included. Lesion detection and characterization were compared between all SS SE-EPI and T2-weighted turbo spin echo (T2w TSE) sets (two-sided Fisher's exact test). Image quality and lesion conspicuity were compared for SS SE-EPI sets using rank order statistic (RIDIT). Reference standard comprised of surgery, biopsy and/or follow-up. RESULTS: Reference standard demonstrated 18 benign and 43 malignant FLLs. Best lesion detection (p<0.05) was achieved with non-contrast-enhanced SS SE-EPI. Lesion characterization was best using all T2w TSE sequences. Best image quality and lesion conspicuity (p<0.05) was achieved with non-contrast-enhanced SS SE-EPI. CONCLUSION: Non-contrast-enhanced SS SE-EPI was best for lesion detection. SS SE-EPI sequences were not useful for lesion characterization (differentiation between benign and malignant lesions). Unenhanced SS SE-EPI did not allow differentiation especially as many benign FLLs were hyperintense on the highest b-value images. Combining unenhanced and SPIO-enhanced SS SE-EPI performed better but still was not clinically useful due to variable degree of uptake and vascular pooling of SPIO for (especially) benign FLLs. T2w TSE with SPIO-enhancement was needed for characterization.


Assuntos
Neoplasias Colorretais/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Óxido Ferroso-Férrico , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
J Dermatol Sci ; 53(1): 26-33, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18782659

RESUMO

BACKGROUND: Loss of TGF-beta growth control is considered as a hallmark of several human neoplasms including melanoma. Resistance of cancer cells to TGF-beta has been linked to mutations in proteins involved in the TGF-beta pathway. In melanoma such mutations have not been observed. C-Ski and SnoN, two structurally and functionally highly homologous proteins, are known as negative regulators in the TGF-beta signaling pathway. C-Ski and SnoN expression levels and subcellular localization have been associated with clinicopathological parameters and tumour progression in several human malignancies. In melanoma cell lines, high c-Ski and SnoN expression levels have been described. OBJECTIVE: The objective of this study was to evaluate the clinical value of c-Ski and SnoN expression in primary cutaneous melanoma. METHODS: We evaluated c-Ski and SnoN expression by immunohistochemical staining in 120 primary melanomas. Possible associations between c-Ski and SnoN staining patterns and clinicopathological parameters were analyzed. RESULTS: Nuclear c-Ski expression was significantly associated with thicker and ulcerated tumours. The percentage of SnoN positivity was higher in ulcerated tumours and in the sentinel node positive group. CONCLUSION: These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Melanoma/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Cutâneas/metabolismo , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/patologia , Fator de Crescimento Transformador beta/metabolismo
20.
J Magn Reson Imaging ; 27(1): 117-24, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18050350

RESUMO

PURPOSE: To prospectively compare single-shot spin-echo echo-planar imaging (SSSE-EPI) using b = 0, 10, 150, and 400 seconds/mm(2) with standard MRI techniques after intravenous super paramagnetic iron oxide (SPIO) in the detection and characterization of focal liver lesions with focus on small (<10 mm) focal liver lesions. MATERIALS AND METHODS: A total of 25 patients suspected for colorectal liver metastases were included. Number of detected lesions was evaluated. Image quality was compared between SSSE-EPI sequence and post-SPIO (fat-suppressed T1-weighted [T1w] gradient echo [GE], T2-weighted [T2w] turbo spin echo [TSE] and T2* GE) sequences using rank order statistic (RIDIT). Lesion characterization was performed for SSSE-EPI and for all remaining sequences pre- and post-SPIO. Reference standard comprised surgery, biopsy, and/or follow-up. RESULTS: Reference standard demonstrated 25 hemangiomas and 70 metastases. Best lesion detection respectively best image quality (P < 0.05) was achieved with SSSE-EPI (b = 10 seconds/mm(2)) post-SPIO T1w GE and T2w turbo spin echo. Lesion characterization using all sequences pre- and post-SPIO performed best for lesion characterization compared with SSSE-EPI. CONCLUSION: This preliminary study shows the potential of SSSE-EPI as a stand-alone sequence for the detection of liver hemangiomas and metastases when compared with SPIO-enhanced imaging. Sequences pre- and post-SPIO are needed for qualitative lesion characterization.


Assuntos
Neoplasias Colorretais/patologia , Meios de Contraste/administração & dosagem , Imagem Ecoplanar/métodos , Ferro/administração & dosagem , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/métodos , Óxidos/administração & dosagem , Dextranos , Feminino , Óxido Ferroso-Férrico , Humanos , Injeções Intravenosas , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade , Imagem Corporal Total
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