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1.
Ann Surg Oncol ; 26(3): 815-820, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30556120

RESUMO

BACKGROUND: OncotypeDX recurrence score (RS)® has been found to predict recurrence and disease-free survival in patients with node negative breast cancer. Whether RS is useful in guiding locoregional therapy decisions is unclear. We sought to evaluate the relationship between RS and lymph node burden. METHODS: Patients with invasive breast cancer who underwent sentinel lymph node dissection from 2010 to 2015 were identified from a prospectively maintained database. Patients were excluded if they were clinically node positive or if they received neoadjuvant chemotherapy. RS was classified as low (< 18), intermediate (18-30), or high (> 30). The association between RS, lymph node burden, and disease recurrence was evaluated. Statistical analyses were performed in R version 3.4.0; p < 0.05 was considered significant. RESULTS: A positive SLN was found in 168 (15%) of 1121 patients. Completion axillary lymph node dissection was performed in 84 (50%) of SLN-positive patients. The remaining 84 (50%) patients had one to two positive SLNs and did not undergo further axillary surgery. RS was low in 58.5%, intermediate in 32.6%, and high in 8.9%. RS was not associated with a positive SLN, number of positive nodes, maximum node metastasis size, or extranodal extension. The median follow-up was 23 months. High RS was not associated with locoregional recurrence (p = 0.07) but was significantly associated with distant recurrence (p = 0.0015). CONCLUSIONS: OncotypeDX RS is not associated with nodal burden in women with clinically node-negative breast cancer, suggesting that RS is not useful to guide decisions regarding extent of axillary surgery for these patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Testes Genéticos/métodos , Recidiva Local de Neoplasia/patologia , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/cirurgia , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Linfonodo Sentinela/metabolismo , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
2.
Clin Radiol ; 72(3): 266.e1-266.e6, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28341031

RESUMO

AIM: To determine if the rate and timing of a second breast cancer event (SBCE) in women with a personal history of breast cancer varies by disease subtype or breast imaging method. MATERIALS AND METHODS: A retrospective review was performed of women with a SBCE from January 2006 to December 2010 at a single institution. Data analysed included oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status of the primary and second breast cancers; mammographic and ultrasound (US) features from SBCE; and the time interval between both events. RESULTS: Of 207 patients diagnosed with a SBCE, the median age at first diagnosis was 50.6 years, range 24.8 to 80.2; at second diagnosis was 56.2 years, range 25.8 to 87.9. Eleven percent of SBCE were diagnosed >10 years after the primary cancer diagnosis. The median time between the first and second diagnosis for ER-positive patients was 2.7 years (range 0.7-17.4 years); and 1.9 years for ER-negative patients, (range 0.4-23.4 years; p<0.002). Patients with triple-negative breast cancer (TNBC) had a shorter time between diagnoses than others (p=0.0003). At 3, 5, and 10 years, 85%, 92%, and 97% of ER-negative and 54%, 81%, and 95% of ER-positive tumours, respectively, had recurred. ER-negative tumours and TNBC were more likely to be visible at US. CONCLUSION: There may be a role for customised imaging surveillance of women with a personal history of breast cancer (PHBC) after 10 years. Further studies are necessary to determine if US may be valuable in the surveillance of patients with ER-negative and TNBC tumours.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Neoplasias da Mama/sangue , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Vigilância da População , Receptor ErbB-2/sangue , Receptores de Estrogênio/sangue , Receptores de Progesterona/sangue , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Adulto Jovem
3.
Clin Radiol ; 71(6): 515-22, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27012496

RESUMO

AIM: To determine the ability of magnetic resonance imaging (MRI) in detecting tumour-free margins from the internal os (IO). MATERIALS AND METHODS: A database search yielded 79 women with early-stage cervical cancer who underwent radical hysterectomy and preoperative MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI in assessment of ≤5 and >5 mm IO involvement were calculated with histopathological surgical specimen findings considered to be the reference standard. A main and subset analysis was performed. The subset analysis included only those patients who would have been considered for radical trachelectomy. RESULTS: For predicting a distance between the tumour and the IO of ≤5 mm, MRI had a sensitivity of 73%, a specificity of 98.3%, a PPV of 95%, a NPV of 88.1%, and an accuracy of 89.8% for the main analysis, and sensitivity of 81.8%, a specificity of 93.2% a PPV of 69.2% a NPV of 96.5% and an accuracy of 91.4% for the subset analysis. CONCLUSION: MRI has high specificity, NPV, and accuracy in detecting tumour from the IO, making MRI suitable for treatment planning in patients desiring trachelectomy to preserve fertility.


Assuntos
Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Imageamento por Ressonância Magnética/métodos , Margens de Excisão , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Adulto , Colo do Útero/cirurgia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Gradação de Tumores , Cuidados Pré-Operatórios/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
4.
Ann Oncol ; 26(10): 2125-32, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26199392

RESUMO

BACKGROUND: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. PATIENTS AND METHODS: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. RESULTS: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. CONCLUSIONS: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population. CLINICALTRIALSGOV: NCT00936936.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Transplante de Células-Tronco Hematopoéticas , Neoplasias do Mediastino/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Retroperitoneais/terapia , Neoplasias Testiculares/terapia , Adolescente , Adulto , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Criança , Cisplatino/administração & dosagem , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Masculino , Neoplasias do Mediastino/mortalidade , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/patologia , Terapia de Salvação , Taxa de Sobrevida , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Transplante Autólogo , Adulto Jovem , Gencitabina
5.
Ann Oncol ; 26(12): 2490-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26416896

RESUMO

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkin's lymphomas. Patients who present with advanced disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL. PATIENTS AND METHODS: This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data. RESULTS: The Kaplan-Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years. CONCLUSION: Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions. CLINICALTRIALSGOV: NCT00506129.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Adulto Jovem
6.
Invest New Drugs ; 32(5): 969-75, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24875133

RESUMO

BACKGROUND: Melanoma cell lines treated with decitabine show upregulation of cancer antigens, and interferon-α upregulates MHC Class I antigens in cancer cells, leading to enhanced T-cell recognition and T-cell mediated tumor apoptosis. We evaluated the synergy between the hypomethylating effects of decitabine and the immunomodulatory effects of interferon in a combination regimen administered to advanced melanoma patients in a phase 1 trial. METHODS: Patients with one prior systemic therapy were eligible. Using a modified 3 + 3 design, patients received escalating doses of decitabine and pegylated interferon α-2b (PEG-IFN) during every 28-day treatment cycle. Global DNA methylation was measured on days 1 and 5 of cycles 1 and 3. Cytokine profiling and quantification of T-cell subpopulations by FACS were performed at baseline and cycle 3. RESULTS: Seventeen patients were assigned to one of four dose levels. Decitabine 15 mg/m2/d + PEG-IFN 3 µg/kg was the maximum tolerated dose (MTD). Grade 3/4 cytopenias were seen across all dose levels: anemia (1), neutropenia (7), and thrombocytopenia (2). One patient remained progression-free for 37 weeks. The other 16 patients progressed at or before 12 weeks. Median overall survival was 39 weeks. Hypomethylation was seen at all dose levels. Due to treatment-induced lymphocytopenia, absolute changes in T-cell populations post-treatment were too small to be meaningfully interpreted. CONCLUSIONS: The response to this combination regimen was characterized by significant myelosuppression, particularly neutropenia. Although disappointing efficacy and slow accrual led to early closure of the trial, hypomethylation showed pharmacodynamic evidence of a therapeutic effect of decitabine at all dose levels.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Melanoma/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Azacitidina/análogos & derivados , Metilação de DNA , Decitabina , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Contagem de Leucócitos , Masculino , Dose Máxima Tolerável , Melanoma/imunologia , Melanoma/metabolismo , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Subpopulações de Linfócitos T/imunologia
7.
Br J Dermatol ; 169(3): 549-54, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23627639

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the white population. It is an important driver of healthcare costs and causes significant morbidity. Topical imiquimod is a good noninvasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative. OBJECTIVES: To determine whether tumour thickness in sBCC is a predictor of treatment failure. METHODS: We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod five times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification. RESULTS: Among nonrecurrent cases the median tumour thickness was 0·26 mm (range 0·09-0·61), while for recurrent cases the median tumour thickness was 0·57 mm (range 0·41-1·41, P < 0·0001). Among lesions ≤ 0·40 mm in thickness, none recurred, whereas for lesions > 0·40 mm the recurrence rate was 58% (P < 0·0001). CONCLUSIONS: We recommend the use of tumour thickness to define the superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.


Assuntos
Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/patologia , Feminino , Humanos , Imiquimode , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Falha de Tratamento , Resultado do Tratamento
8.
Radiography (Lond) ; 29(6): 975-979, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37572571

RESUMO

INTRODUCTION: The purpose of our study was to compare the performance of 2D (FFDM) against 3D (FFDM plus DBT) examinations in the post-treatment surveillance of asymptomatic breast cancer survivors. METHODS: A list of women with a history of breast cancer who underwent screening mammography (2D or 3D) from 5/2017 to 5/2020 was retrieved. A total of 20,210 examinations were identified and performance metrics were compared. RESULTS: There were no statistically significant difference in cancer detection rate (CDR) (p = 0.38), recall rate (RR) (p = 0.087), or positive predictive value (PPV) (p = 0.74) between 2D vs. 3D examinations. Stratification by breast tissue identified no statistically significant difference in CDR (p = 0.581 and p = 0.428), RR (p = 0.230 and p = 0.205), or PPV (p = 0.908 and p = 0.721) between fatty/scattered and heterogeneous/extremely dense breast tissue when comparing 2D vs 3D examinations. Stratification by age did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased with 2D vs. 3D examinations in the 60-69 years group (p = 0.021). Stratification by race did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased with 3D vs. 2D examinations in white women (p = 0.036). Stratification by laterality (bilateral vs. unilateral post mastectomy) did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased in 2D vs. 3D examinations in unilateral studies (p = 0.009). CONCLUSION: For asymptomatic women with a history of breast cancer, there is no evidence that the addition of DBT to FFDM improves CDR, RR, or PPV. IMPLICATIONS FOR PRACTICE: More studies are needed concerning screening methodologies supplementing FFDM in the screening regimens of breast cancer survivors.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Mamografia/métodos , Estudos Retrospectivos , Densidade da Mama , Programas de Rastreamento , Detecção Precoce de Câncer/métodos , Mastectomia
9.
Breast Cancer Res Treat ; 131(1): 41-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21331622

RESUMO

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.


Assuntos
Neoplasias da Mama/patologia , Metaplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Metaplasia/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
11.
Reprod Biomed Online ; 19(3): 300-13, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19778474

RESUMO

Advances in proteomic technology have enabled contaminant proteins to be identified from complex protein mixtures. The purity of two purified urinary gonadotrophin products, human menopausal gonadotrophin (u-HMG) and human FSH (u-hFSH), was compared with a preparation of recombinant human FSH (r-hFSH). After separation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot analysis showed that the recombinant preparation contained only FSH, whereas the urine-derived preparations exhibited several non-FSH or LH-related bands. These urinary components were further investigated by a proteomic approach using two-dimensional SDS-PAGE followed by mass spectrometric identification. The proteomic approach detected a total of 23 non-gonadotrophin-related proteins, at variable levels in different batches of the urine-derived preparations. Of these, 16 co-purified proteins have not been previously reported to be present in urine-derived gonadotrophins. These results indicate that the process used to purify urinary gonadotrophins may not remove all non-gonadotrophin proteins. By using a comprehensive proteomic approach, it has been shown that the recombinant FSH preparation has greater purity than either of the urine-derived preparations.


Assuntos
Contaminação de Medicamentos , Menotropinas/análise , Avaliação de Medicamentos , Eletroforese em Gel de Poliacrilamida , Hormônio Foliculoestimulante/análise , Hormônio Foliculoestimulante/normas , Humanos , Menotropinas/metabolismo , Menotropinas/normas , Menotropinas/urina , Proteínas/isolamento & purificação , Proteínas/metabolismo , Proteômica , Proteínas Recombinantes/análise , Proteínas Recombinantes/normas , Urina/química
12.
Spinal Cord ; 47(6): 496-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19172154

RESUMO

STUDY DESIGN: Cross-sectional pilot study. OBJECTIVES: To explore correlates of body image among women with spinal cord injury (SCI), within the framework of Cash's cognitive behavioral model of body image. SETTING: Hamilton, Ontario, Canada. METHODS: Women with SCI (N=11, 64% with tetraplegia) reported their functional and appearance body image (Adult Body Satisfaction Questionnaire). A 3-day recall of leisure time physical activity (LTPA), three measures of body composition (that is, weight, waist circumference, body fat) and several demographic variables were assessed as potential correlates. RESULTS: Appearance satisfaction was negatively correlated with all three measures of body composition and positively correlated with years postinjury. Functional satisfaction was positively correlated with years postinjury, and negatively correlated with various LTPA variables. CONCLUSION: Functional and appearance body image may improve with time following SCI. Body composition may impact satisfaction with physical appearance for some women. The negative relationship between LTPA and functional satisfaction merits further examination, as functional dissatisfaction may motivate individuals to engage in certain types and intensities of LTPA. Correlates of body image differ between appearance and functional satisfaction. Future research should examine appearance and functional satisfaction separately among women with SCI.


Assuntos
Imagem Corporal , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/psicologia , Adulto , Composição Corporal/fisiologia , Feminino , Humanos , Atividade Motora , Projetos Piloto , Estatísticas não Paramétricas , Inquéritos e Questionários
13.
Br J Surg ; 95(4): 433-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18161887

RESUMO

BACKGROUND: Neoadjuvant chemotherapy for breast cancer reduces tumour cellularity, the percentage of the primary tumour area that is composed of invasive tumour cells. Minimal residual tumour cellularity (5 per cent or less of tumour area composed of invasive tumour cells) may be associated with an increased risk of false-negative intraoperative margins. The aim of this study was to evaluate the incidence of minimal residual tumour cellularity after neoadjuvant chemotherapy and its impact on the frequency of false-negative margins and conversion from breast-conserving surgery to mastectomy. METHODS: The final pathology slides of 510 patients who had surgery after neoadjuvant chemotherapy were reviewed. RESULTS: Of 396 patients with residual invasive breast cancer after neoadjuvant chemotherapy, 100 specimens (25.3 per cent) had minimal residual cellularity; this was more frequent in patients with invasive lobular carcinoma (17.0 versus 5.1 per cent; P < 0.001) or well and moderately differentiated carcinoma (68.0 versus 52.4 per cent; P = 0.007). Among 149 patients who had initial breast-conserving surgery, false-negative intraoperative margin rates were 23 per cent in specimens with minimal and 13.8 per cent in those with higher residual cellularity (P = 0.210). There was no significant difference in the rate of conversion to mastectomy between the groups. CONCLUSION: Minimal residual cellularity after neoadjuvant chemotherapy occurred in about 25 per cent of specimens, but did not alter the rate of false-negative intraoperative margins.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Br J Dermatol ; 159(1): 105-12, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18489588

RESUMO

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS), variants of cutaneous T-cell lymphoma, may arise from antigen-driven clonal expansion and accumulation of helper-memory T cells. Superantigens from Staphylococcus aureus can stimulate T cells. OBJECTIVES: (i) To determine the prevalence of S. aureus carriage in nares and skin in patients with MF/SS compared with historical rates in other conditions. (ii) To determine whether eradication of S. aureus carriage is associated with clinical improvement. Methods Skin and nares cultures were performed prospectively. Patients with positive nares and skin cultures were treated with oral antibiotics and intranasal mupirocin 2% and samples were taken for reculturing at 3 days, 4 weeks and 8 weeks. An exact binomial test was used to compare the carriage rates among different groups. RESULTS: Among 106 patients with MF/SS, 67 (63%) had skin colonization and 57 (54%) had nasal colonization. Staphylococcus aureus was isolated from 44 patients, 33 (31%) each from skin and nares. Colonization was highest in erythrodermic SS (48%), similar to atopic dermatitis (64%), and lowest in MF without erythroderma (26%), psoriasis (21%), and the general population (10%). Oral and topical antibiotics eradicated S. aureus colonization in nares in 28 of 33 (85%) patients and in MF skin lesions in 30 of 33 (91%) patients at 4-8 weeks, with rapid clinical improvement seen in 58% of S. aureus-colonized patients. CONCLUSIONS: Staphylococcal carriage in nares and skin lesions of patients with MF is similar to that in atopic dermatitis. Eradication of staphylococci from the skin is possible with treatment and was associated with clinical improvement.


Assuntos
Antibacterianos/administração & dosagem , Linfoma Cutâneo de Células T/microbiologia , Mupirocina/administração & dosagem , Micose Fungoide/microbiologia , Cavidade Nasal/microbiologia , Neoplasias Cutâneas/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Infecções Cutâneas Estafilocócicas/microbiologia , Resultado do Tratamento
15.
Int J Gynecol Cancer ; 18(1): 146-51, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17466036

RESUMO

The objective of our study was to evaluate the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p27, and mammalian target of rapamycin (mTOR) expressions in women with progesterone-responsive and refractory endometrial hyperplasia (EH) samples and to determine if these markers could be associated with response or used as potential targets for treatment. Thirty-eight matched pre- and posttreatment pairs of paraffin-embedded endometrial biopsies were obtained from patients with EH. Immunohistochemical analysis for PTEN, p27, and phospho-mTOR were performed on all samples. Median age at diagnosis was 49 years (20-79 years). Median treatment interval was 3 months (1-12 months). Sixteen patients (42.1%) had complete resolution of their hyperplasia (responders), and 22 (57.9%) had persistent hyperplasia (nonresponders) after treatment with progesterone. In the pretreatment samples, no markers were found to predict nonresponders. In posttreatment samples, loss of PTEN expression with phospho-mTOR expression was observed in more nonresponders than responders (40.9% vs 6.3%; P= 0.03). Phospho-mTOR overexpression was found in 63.6% of nonresponders. We found that persistent hyperplasia refractory to progesterone therapy was associated both with the loss of PTEN and with the loss of phosphorylation of mTOR. In select cases of non-responsive progesterone refractory EH, a rational target for treatment may involve the mTOR pathway.


Assuntos
Cromossomos Humanos Par 10/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Hiperplasia Endometrial/tratamento farmacológico , Deleção de Genes , PTEN Fosfo-Hidrolase/genética , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Proteínas Quinases/metabolismo , Adulto , Idoso , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Fosforilação/efeitos dos fármacos , Serina-Treonina Quinases TOR
16.
Bone Marrow Transplant ; 52(1): 28-33, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27595282

RESUMO

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.


Assuntos
Cloridrato de Bendamustina/administração & dosagem , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
17.
Curr Med Res Opin ; 21(12): 1969-76, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16368048

RESUMO

BACKGROUND: A commercial preparation of recombinant human chorionic gonadotrophin (r-hCG, Ovitrelle) was launched in 2001. Generally, hCG is available in two formats: human chorionic gonadotrophin (u-hCG), derived from the urine of pregnant females, and r-hCG produced by DNA based biotechnology. METHOD: The analytical characteristics of a highly purified u-hCG (Gonasi HP) were assessed and compared, for the first time, with the recombinant derived r-hCG (Ovitrelle). Gonasi HP is produced by extracting and purifying hCG from urine to obtain a specific bioactivity of 5000 IU/mg protein. Ovitrelle is produced via a recombinant derived mammalian cell line and purified to obtain a specific activity of 26 000 IU/mg. RESULTS AND CONCLUSION: It has been documented that commercially available u-hCG preparations can contain a number of urine derived protein contaminants as well as hCG related metabolites. This is also the case for Gonasi HP, where hCG related molecules and other proteins were found to be present, including epidermal growth factor (EGF) and eosinophil derived neurotoxin (EDN). It was also demonstrated that this preparation contained high levels of oxidised hCG. r-hCG was confirmed to be essentially intact hCG, free from contaminant proteins and with very low levels of oxidised hCG.


Assuntos
Gonadotropina Coriônica/análise , Gonadotropina Coriônica/química , Gonadotropina Coriônica/urina , Cromatografia Líquida de Alta Pressão , Densitometria , Eletroforese em Gel de Poliacrilamida , Neurotoxina Derivada de Eosinófilo/análise , Fator de Crescimento Epidérmico/análise , Humanos , Immunoblotting , Peso Molecular , Proteínas Recombinantes/análise
18.
Curr Med Res Opin ; 21(6): 899-905, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15969890

RESUMO

OBJECTIVE: Pharmaceutical preparations of human menopausal gonadotrophin (hMG), urine-derived follicle-stimulating hormone (u-FSH) and highly purified u-FSH (u-FSH-HP) have been available since the early 1960s and the mid 1980s and 1990s, respectively. Another commercial preparation of u-FSH-HP, Folyrmon P, was launched in Japan in 1999. The aim of this study is to assess the purity of Folyrmon P and to compare it with Fertinorm-P, another commercial preparation of u-FSH-HP that has been available since 1993. METHODS: Folyrmon P and Fertinorm-P were assessed for total protein content, biological activity, immunological activity, specific activity, purity and levels of protein contamination. RESULTS: Folyrmon P, which is extracted from the urine of post-menopausal women, has a specific activity of between 4000 and 5000 IU/mg, while Fertinorm-P, which is also manufactured from the urine of post-menopausal women, has a specific activity of at least 10,000 IU/mg. It has been well documented that commercially available hMG and u-FSH preparations can contain a number of urine-derived protein contaminants. This also proves to be the case for Folyrmon P, in which contaminant proteins other than FSH were shown to be present. It was also demonstrated that both preparations, Folyrmon P and Fertinorm-P, contained high levels of oxidized FSH. CONCLUSIONS: The low specific activity and high level of contaminants in Folyrmon P indicate that this u-FSH is not highly purified. Overall, Fertinorm-P, with higher specific activity and lower levels of contaminant proteins, appears to be of higher quality compared with Folyrmon P.


Assuntos
Hormônio Foliculoestimulante/análise , Preparações Farmacêuticas/análise , Feminino , Hormônio Foliculoestimulante/isolamento & purificação , Hormônio Foliculoestimulante/urina , Humanos , Pós-Menopausa
19.
Aust Vet J ; 83(5): 276-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15957387

RESUMO

Recurrent flank alopecia is described in a 2-year-old, male, neutered Tibetan Terrier with concurrent atopic dermatitis. The diagnosis of recurrent flank alopecia was made after 3 consecutive years of localised, winter-onset alopecia. The diagnosis was based on history, compatible clinical signs and supportive histopathology. The diagnosis was complicated by the presence of concurrent pruritic dermatitis. To our knowledge this is the first report of recurrent flank alopecia in this breed.


Assuntos
Alopecia/veterinária , Doenças do Cão/diagnóstico , Alopecia/diagnóstico , Alopecia/patologia , Animais , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/patologia , Dermatite Atópica/veterinária , Doenças do Cão/patologia , Cães , Masculino , Recidiva , Estações do Ano
20.
Aust Vet J ; 83(5): 280-2, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15957388

RESUMO

An 8-month-old, crossbred dog, presented with a painful, swollen face. The problem was of 4 weeks duration and had not responded to antibiotics. A diagnosis of canine juvenile cellulitis was based on the clinical presentation and supportive cytological and histopathological changes. Attempts to identify canine distemper virus were not successful. Complete resolution occurred with glucocorticoid therapy. This is the first report of canine juvenile cellulitis in a dog of this age.


Assuntos
Celulite (Flegmão)/veterinária , Doenças do Cão/diagnóstico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Fatores Etários , Alopecia/etiologia , Alopecia/veterinária , Animais , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/patologia , Diagnóstico Diferencial , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Resultado do Tratamento
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