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1.
Breast Cancer Res Treat ; 117(3): 483-95, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18819002

RESUMO

PURPOSE: The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530-536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. METHODS: We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). RESULTS: The 5-year OS was 82 +/- 5% in poor (48%) and 97 +/- 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P = 0.021). The 5-years DMFP was 78 +/- 6% in poor and 98 +/- 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 +/- 5% and 94 +/- 3% (HR 10.7; 95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 +/- 6% in poor and 86 +/- 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. CONCLUSION: The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica , Adulto , Área Sob a Curva , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Curva ROC , Fatores de Risco
2.
Plast Reconstr Surg ; 122(6): 1747-1755, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19050527

RESUMO

BACKGROUND: Most data on secondary intention healing of skin cancer defects in the head and neck are empirical and descriptive. This study statistically evaluates the prognostic value of several wound characteristics and location on the final cosmetic result of skin defects left to heal by secondary intention after tumor removal. METHODS: A chart review of all facial reconstructions using secondary intention healing performed in one center between 1992 and 2001 was undertaken. Patient and wound characteristics were analyzed. For analysis of cosmetic outcome, the most recent photographs of the scars were assessed by three independent raters using a categorical judgment scale. RESULTS: There were a total of 89 patients with 95 wounds. Forty-three percent of the wounds (41 of 95) healed with an "excellent" outcome. In the univariate analysis, the rating excellent was given more often to scars derived from wounds that were small and superficial and that were located in concave areas of the face, in particular, near the medial canthus and medial cheek. Multivariable logistic regression revealed independent associations of an excellent cosmetic outcome with wound size and contour of wound surface only. CONCLUSION: This is the first study presenting statistical evidence of what has been known empirically for a long time: wounds in concave areas of the face that are left to heal by secondary intention have a high chance of healing with an excellent cosmetic outcome, especially if these wounds are small, superficial, and located near the medial canthus and medial cheek.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Cicatrização , Idoso , Idoso de 80 Anos ou mais , Cicatriz/patologia , Face/patologia , Face/cirurgia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Nasais/patologia , Neoplasias Nasais/cirurgia , Variações Dependentes do Observador , Prognóstico , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Resultado do Tratamento
3.
Br J Cancer ; 99(3): 398-403, 2008 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-18648365

RESUMO

The tumour antigen PReferentially expressed Antigen of MElanoma (PRAME) is expressed in a variety of malignancies, including breast cancer. We have analysed PRAME gene expression in relation to clinical outcome for 295 primary breast cancer patients. Kaplan-Meier survival curves show a correlation of PRAME expression levels with increased rates of distant metastases and decreased overall patient survival. This correlation existed both for the entire patient group (n=295) and for the subgroup of patients (n=185) who did not receive adjuvant chemotherapy. Multivariable analysis indicated that PRAME is an independent marker of shortened metastasis-free interval in patients who did not receive adjuvant chemotherapy. PRAME expression was associated with tumour grade and negative oestrogen receptor status. We conclude that PRAME expression is a prognostic marker for clinical outcome of breast cancer, independent of traditional clinicopathological markers.


Assuntos
Antígenos de Neoplasias/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Humanos , Análise Multivariada , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
4.
Diabetes Technol Ther ; 10(2): 57-68, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18260769

RESUMO

Continuous glucose monitors may be valuable tools for improving glycemic control and avoiding hypoglycemia in patients with diabetes. To this goal, sensor readings must adequately reflect the actual blood glucose, emphasizing the need for solid accuracy assessment methods for continuous glucose sensor readings. Analysis of continuous glucose data is challenging, and despite many efforts there still is no all-embracing method to overcome the obstacles in the assessment of continuous data. In this review we disclose the weaknesses of currently available methods and propose a guideline for sensor accuracy assessment and comparison. For accuracy assessment it is best to first plot the sensor readings against the reference values and draw a line of identity, visualizing the degree of agreement. Thereafter data pairs should be given in a Bland-Altman plot to detect a possible relationship between the difference and the mean. The next step is to calculate the absolute relative difference over all paired readings together and per glucose range. A possible lag time between the measurements of both methods can be detected by combined curve fitting. Finally, sensitivity and positive predictive value for detecting hypoglycemia are important indicators of the sensors' performance. For comparing the accuracy between different glucose sensors it is best to use indirect comparison against blood glucose, rather than direct comparison methods, since none of the current glucose sensors is accurate enough to be considered the reference value.


Assuntos
Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Guias como Assunto , Humanos , Hipoglicemia/sangue , Hipoglicemia/prevenção & controle , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Cancer Chemother Pharmacol ; 61(6): 1075-81, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17639394

RESUMO

PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Adutos de DNA/efeitos dos fármacos , Neoplasias/metabolismo , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapêutico , Terapia Combinada , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Contagem de Leucócitos , Mucosa Bucal/citologia , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Valor Preditivo dos Testes
6.
Eur J Surg Oncol ; 34(5): 501-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17555911

RESUMO

AIM: To compare the breast cancer stages found during MG alone surveillance in women at increased risk with those detected in a program where MRI was added. METHODS: Stage results of in a retrospective MG alone study of prospectively followed patients, compared with the pooled stage results of breast cancers MG/MRI surveillance. RESULTS: One hundred and-fifty-one patients were detected with a first or contralateral breast cancer. Interval cancers were diagnosed in 56% of the BRCA1, 42% of the BRCA2 and 28% of the non-BRCA carriers. A considerable proportion of the breast cancers were detected with breast self-examination alone: 41%, 27% and 31% respectively. Nevertheless the established goals for biennial population screening were reached, except for the BRCA2 carriers, but this group was small. Comparison with pooled data from published MG/MRI surveillance studies did not show significant differences in the stages, except for the BRCA2 carriers. CONCLUSION: Breast cancers detected in a MG alone surveillance program for women at increased risk fulfill most goals set for population screening except for the BRCA2 carriers. Breast self-examination appears to be a valuable additional detection method especially for BRCA1 carriers, who are at risk of developing a highly proliferating breast cancer.


Assuntos
Neoplasias da Mama/patologia , Autoexame de Mama , Predisposição Genética para Doença , Vigilância da População , Adulto , Neoplasias da Mama/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco
7.
Histopathology ; 51(6): 763-73, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18042066

RESUMO

AIMS: Goblet cell carcinoid is a poorly understood tumour of the appendix. The aim of this study was to determine whether it should be regarded as a separate entity or as a variant of classical carcinoid. METHODS AND RESULTS: The immunohistochemical expression pattern of 21 markers and the mutation status of KRas codon 12 were determined in 16 goblet cell carcinoids and compared with 14 classical carcinoids, 19 colonic adenocarcinomas and 10 appendiceal mucinous cystadeno (carcino)mas. The results were subjected to a stepwise linear discriminant analysis. Goblet cell carcinoids were significantly different from the control groups. The most important markers for discriminating between the groups were CEA (classical carcinoid versus all others), KRas mutation (present in all mucinous cystadeno (carcino)mas), beta-catenin (goblet cell carcinoid versus left sided colonic adenocarcinoma) and chromogranin (goblet cell carcinoid versus right sided colonic adenocarcinoma). Expression of Math1 and HD5 was similar in goblet cell carcinoid and colonic adenocarcinoma but absent in classical carcinoid. CONCLUSION: The results suggest that goblet cell carcinoids should be regarded as a separate entity. The formerly used term 'crypt cell carcinoma' may be more appropriate because it reflects the more aggressive clinical behaviour of these tumours as well as their greater similarity to adenocarcinomas rather than to carcinoids.


Assuntos
Neoplasias do Apêndice/patologia , Biomarcadores Tumorais/análise , Tumor Carcinoide/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Neoplasias do Apêndice/genética , Neoplasias do Apêndice/metabolismo , Tumor Carcinoide/genética , Tumor Carcinoide/metabolismo , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Mutação , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética
8.
Acta Otolaryngol ; 126(12): 1315-20, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17101594

RESUMO

CONCLUSION: Annual post-treatment screening of head and neck squamous cell carcinoma (HNSCC) patients for second primary lung cancer and metastatic recurrence appeared to form no major burden for head and neck cancer patients. A majority of patients regard the annual chest X-ray as a reassurance. Given these results a more intensive screening program seems psychologically justifiable for this group. OBJECTIVE: To assess the psychological impact of annual post-treatment screening for second primary lung cancer and metastases in HNSCC patients. PATIENTS AND METHODS: In a cohort of 106 patients, 68 men and 38 women, with a mean age of 56, the impact of the yearly chest radiograph was evaluated by means of a nine-item questionnaire. RESULTS: In all, 90% of the patients were in favor of annual post-treatment screening, 2% would not like to receive this screening, and 8% had no preference. A majority (98%) considered the screening as an extra medical check and 76% felt reassured. Although 21% of the patients were very nervous about the outcome of the screening, only 3% wanted to avoid the yearly chest X-ray for this reason.


Assuntos
Carcinoma de Células Escamosas/psicologia , Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/psicologia , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/secundário , Radiografia Torácica/psicologia , Estresse Psicológico/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente
9.
Eur Radiol ; 16(12): 2842-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16924440

RESUMO

Breast cancers in BRCA1 gene mutation carriers often have specific histologic features: grade III tumors with pushing margins. Our purpose was to compare the mammographic and histologic features of breast cancers in carriers with those in age-matched sporadic controls. The features of breast cancers in 27 BRCA1 carriers found during annual surveillance were compared to those in 107 age-matched sporadic controls. The carriers had no (classic) spiculated mammographic lesions, a high percentage of well-defined masses and hardly any masses with microcalcifications, whereas the controls had significantly fewer well-defined ones and only in 27% spiculated lesions on the mammogram. The well-defined mammographic tumors correlated in 83% of the carriers and in 70% of the controls with histologic circumscribed tumor margins. Spiculated mammographic lesions in the controls were in 90% grade I or II tumors. DCIS with or without infiltration was seen in 22% of the carriers and in 45% of the controls. In conclusion, breast cancers diagnosed in BRCA1 carriers do not have classic malignant mammographic features. A minority of the young sporadic controls show the classic malignant lesion on the mammogram. Both carriers and controls generally show a good correlation between their mammographic- and histologic tumor pattern.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Genes BRCA1 , Mamografia , Adulto , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Mutação , Vigilância da População
10.
Neurology ; 66(1): 62-8, 2006 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-16401847

RESUMO

OBJECTIVE: To determine the optimal timing of somatosensory evoked potential (SSEP) recordings and the additional value of clinical and biochemical variables for the prediction of poor outcome in patients who remain comatose after cardiopulmonary resuscitation (CPR). METHODS: A prospective cohort study was conducted in 32 intensive care units including adult patients still unconscious 24 hours after CPR. Clinical, neurophysiologic, and biochemical variables were recorded 24, 48, and 72 hours after CPR and related to death or persisting unconsciousness after 1 month. RESULTS: Of 407 included patients, 356 (87%) had a poor outcome. In 301 of 305 patients unconscious at 72 hours, at least one SSEP was recorded, and in 136 (45%), at least one recording showed bilateral absence of N20. All these patients had a poor outcome (95% CI of false positive rate 0 to 3%), irrespective of the timing of SSEP. In the same 305 patients, neuron-specific enolase (NSE) was determined at least once in 231, and all 138 (60%) with a value >33 microg/L at any time had a poor outcome (95% CI of false positive rate 0 to 3%). The test results of SSEP and NSE overlapped only partially. The performance of all clinical tests was inferior to SSEP and NSE testing, with lower prevalences of abnormal test results and wider 95% CI of false positive rates. CONCLUSION: Poor outcome in postanoxic coma can be reliably predicted with somatosensory evoked potentials and neuron-specific enolase as early as 24 hours after cardiopulmonary resuscitation in a substantial number of patients.


Assuntos
Vias Aferentes/fisiopatologia , Encéfalo/fisiopatologia , Coma/diagnóstico , Potenciais Somatossensoriais Evocados/fisiologia , Hipóxia Encefálica/diagnóstico , Hipóxia Encefálica/fisiopatologia , Adulto , Vias Aferentes/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Coortes , Coma/sangue , Coma/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Hipóxia Encefálica/sangue , Masculino , Neurônios/metabolismo , Neurônios/patologia , Estado Vegetativo Persistente/diagnóstico , Estado Vegetativo Persistente/etiologia , Estado Vegetativo Persistente/fisiopatologia , Fosfopiruvato Hidratase/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Tempo
11.
Breast ; 14(4): 310-6, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16085238

RESUMO

Randomized clinical trials (RCT) are the best way to define optimal treatment, but the accrual rates for hardly any trials have been reported. We analyzed retrospectively the participation of patients in eight phase III multicenter RTCs. Out of a total of 738 patients treated in a single institution for operable breast cancer over a 3-year period, 455 patients (62%) were eligible for at least one of the ongoing trials. Overall, 81% of the patients were informed and 47% of the eligible patients consented to participate. The accrual was 100% to a study with an aggressive combined modality treatment arm for patients with a poor prognosis. A low accrual rate was seen in two trials: 6% in the "elderly" trial comparing tamoxifen only with mastectomy and 10% to the "axilla" trial comparing surgery with radiotherapy to the axilla. The clinicians failed to inform most of these patients about the two trials. In the literature seven of the eight trials were reported; two of them (29%) failed to accrue enough patients.


Assuntos
Neoplasias da Mama/cirurgia , Seleção de Pacientes , Papel do Médico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Consentimento Livre e Esclarecido , Estudos Multicêntricos como Assunto , Estudos Retrospectivos
12.
Eur Urol ; 48(2): 239-45, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16005375

RESUMO

OBJECTIVE: To evaluate the long-term survival following brachytherapy and following cystectomy of patients with invasive bladder cancer treated in our institution. PATIENTS AND METHODS: Between 1988 and 2000 108 patients with solitary, organ confined T1-T2 invasive bladder cancer of < or = 5 cm were treated with a transurethral resection, and a course of external beam radiotherapy (30 Gy) followed by 40 Gy brachytherapy. The overall and disease specific survival rates of these patients are compared with those of 77 patients with T1-T2 invasive bladder cancer treated with cystectomy between 1988-2003. RESULTS: The 5/10 year overall survival rates were 62%/50% after brachytherapy and 67%/58% after cystectomy (p = 0.67). The 5/10 year disease specific survival rates were 73%/67% after brachytherapy and 72%/72% after cystectomy (p = 0.28). When adjusted for age, multiplicity, T-stage, N-stage and grade, the 5/10 year overall survival rates were 65%/53% after brachytherapy and 62%/51% after cystectomy, respectively. The adjusted disease specific survival rates were 75%/70% after brachytherapy and 66%/66% after cystectomy. CONCLUSIONS: This study does not provide evidence regarding survival against the use of bladder preservation with brachytherapy for patients with solitary, T1-T2 invasive bladder cancer of < or = 5 cm diameter, seeking bladder-sparing alternatives to radical cystectomy.


Assuntos
Braquiterapia , Cistectomia , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade
13.
Neuropediatrics ; 36(2): 78-89, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15822020

RESUMO

PURPOSE: The aim of this study was to correlate hypoxic-ischemic white matter damage on neonatal MRI with MRI appearance and neurological outcome at the age of 1 1/2 years. PATIENTS AND METHODS: A sequential cohort of infants with periventricular densities on neonatal ultrasound was studied with neonatal MRI. Images of 46 infants with a mean gestational age of 31 weeks were obtained at a mean age of 20 days after birth and at 1 1/2 years. To establish agreement between the neonatal and follow-up MRI (general, motor, and visual scores), the weighted Cohen's kappa test was used. To establish the predictive power of neonatal MRI with respect to the neurologic indices at the age of 1 1/2 years, the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: There was a moderately good to good agreement between the general, motor, and visual neonatal and follow-up MRI scores: weighted kappa = 0.59 (95% CI: 0.44 - 0.74), 0.82 (95% CI: 0.72 - 0.93), and 0.70 (95% CI: 0.56 - 0.84), respectively. Neonatal MRI scores provided a good prediction of the three neurological outcome measures (developmental delay, cerebral palsy, and cerebral visual impairment): sensitivity, specificity, and predictive values were high, with little difference between the three MRI scores. The 32 patients with (nearly) normal neonatal MRI scores were neurologically (nearly) normal at 1 1/2 years on all three outcome measures, whereas 8 patients with seriously abnormal neonatal MRI scores were neurologically abnormal at 1 1/2 years on all three outcome measures. CONCLUSION: Neonatal MRI is able to predict the precise localization and size of perinatal leukomalacia on follow-up MRI and provides a good prediction of neurological outcome at 1 1/2 years.


Assuntos
Ventrículos Cerebrais/patologia , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Leucomalácia Periventricular/patologia , Imageamento por Ressonância Magnética , Fatores Etários , Análise de Variância , Mapeamento Encefálico , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Atividade Motora/fisiologia , Exame Neurológico , Testes Neuropsicológicos , Valor Preditivo dos Testes , Estudos Prospectivos , Desempenho Psicomotor/fisiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Acuidade Visual/fisiologia
14.
Eur J Cancer ; 40(18): 2726-33, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15571954

RESUMO

To assess the benefit of intraventricular chemotherapy, patients with leptomeningeal metastasis (LM) from breast cancer were randomised to treatment including intraventricular (IT) chemotherapy (n=17) or to non-intrathecal (non-IT) treatment (n=18). Appropriate systemic therapy and involved field radiation therapy (RT) were given in both arms. Intention-to-treat analysis showed neurological improvement or stabilisation in 59% of the IT and in 67% of the non-IT group, with median time to progression of 23 weeks (IT) and 24 weeks (non-IT). Median survival of IT patients was 18.3 weeks and 30.3 weeks for non-IT patients (difference 12.9 weeks; 95% Confidence Interval (CI) -5.5 to +34.3 weeks; P=0.32). Neurological complications of treatment occurred in 47% (IT) vs 6% (non-IT) (P=0.0072). In conclusion, standard systemic chemotherapy with involved field RT for LM from breast cancer is feasible. Addition of intraventricular chemotherapy does not lead to survival benefit or improved neurological response, and is associated with an increased risk of neurotoxicity.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias da Mama , Neoplasias Meníngeas/tratamento farmacológico , Metotrexato/administração & dosagem , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Humanos , Injeções Intraventriculares , Injeções Espinhais , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/secundário , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
15.
Eur J Surg Oncol ; 29(8): 682-8, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14511618

RESUMO

AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the abundance of mucus in the abdomen without extra-peritoneal growth. METHODS: Our patients with PMP have been treated with cytoreduction and hyperthermic intraperitoneal chemotherapy since 1996. The clinical and histopathological features of PMP and the relation of these features with disease-free interval and survival were assessed. RESULTS: Sixty-two patients with PMP (24 M/38 F) were studied. Adenomatous mucosal changes were present in 31 patients. In females, the ovaries were normal in 5 patients and pseudomyxoma ovarii was present in 20 patients. Patients with minimal atypia and with 1% focal proliferation or less (n=38) had a better survival (p=0.0008) than those with more focal proliferation (n=14). CONCLUSION: In most patients with PMP the appendix is affected; in females the ovaries are usually also involved. Focal proliferation appears to be a prognostic factor.


Assuntos
Neoplasias Peritoneais , Pseudomixoma Peritoneal , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos , Análise de Sobrevida
16.
Anticancer Res ; 23(2B): 1501-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12820416

RESUMO

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C has been applied following cytoreductive surgery for various peritoneal surface malignancies. The aim of this study was to evaluate heat penetration in the abdomen during 10 HIPEC procedures. MATERIALS AND METHODS: Temperature measurements were taken at 5 levels through the abdominal wall. Core temperature and room temperature were also measured. The relationships between the temperature gradient and room or core temperature were studied. RESULTS: At the start of perfusion, the temperature was estimated on average to be 40.6 degrees C at the first level, then it decreased by 1.7 degrees C (SD 1.0 degree C, p = 0.0001) in the first mm. In outward direction, it decreases by a further 1.5 degrees C per cm (SD 0.3 degree C/cm, p < 0.0001). The core temperature influenced the temperature gradient; the room temperature was not found to be a significant factor. At the end of perfusion, the temperature is estimated on average to be 40.1 degrees C at the first level, then it decreased by 0.8 degree C (SD 0.7 degree C, p = 0.011) in the first mm. In an outward direction, it decreased by a further 1.7 degrees C per cm (SD 0.4 degree C/cm, p = 0.0001). No evidence of an association between the temperature gradient and the room temperature or the core temperature was observed. CONCLUSION: Hyperthermia used during HIPEC procedures has a limited penetration depth. The slope in temperature seems to be related to the core temperature.


Assuntos
Parede Abdominal , Antineoplásicos/administração & dosagem , Temperatura Corporal , Carcinoma/terapia , Hipertermia Induzida , Mitomicina/administração & dosagem , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Humanos , Infusões Parenterais , Masculino , Mitomicina/uso terapêutico , Cavidade Peritoneal , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/cirurgia , Temperatura
17.
J Clin Oncol ; 21(13): 2474-80, 2003 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12829665

RESUMO

PURPOSE: To study the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in patients with recurrent indolent lymphoma. PATIENTS AND METHODS: A total of 109 assessable patients (304 symptomatic sites) were irradiated (53 males and 56 females; median age, 62 years; range, 35 to 93), including 98 patients with follicular lymphoma (43 grade 1 and 55 grade 2), nine extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue-type and two patients with lymphoplasmacytoid lymphoma. Bulky disease (> or =5 cm) was present in 52% of all patients. A median of two prior regimens (range, 0 to 11) preceded LD-IF-RT. The median time since diagnosis was 41 months (range, 2 to 358 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates between treatments within the same patient were compared using the McNemar test. RESULTS: The overall response rate was 92%; complete response was reached in 67 patients (61%), partial response in 34 patients (31%), stable disease in six patients (6%), and progressive disease in two patients (2%). The median time to progression was 14 months. The median time to local progression was 25 months. The 67 patients with complete response showed a median time to progression of 25 months and a median time to local progression of 42 months. None of the factors studied (age, sex, follicular lymphoma grade, radiotherapy regimen, number of previous regimens and previous history, number of positive sites or largest lymphoma diameter) were found to be related to response rate. CONCLUSION: LD-IF-RT is a valuable asset in the management of patients with follicular lymphoma and should be considered in patients with recurrent disease.


Assuntos
Linfoma de Células B/radioterapia , Linfoma Folicular/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Relação Dose-Resposta à Radiação , Feminino , Humanos , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sobrevida , Resultado do Tratamento
18.
Br J Cancer ; 88(7): 1091-4, 2003 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-12671691

RESUMO

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral blood.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Células Neoplásicas Circulantes , Antígenos de Neoplasias/genética , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/genética , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Queratinas/genética , Metástase Neoplásica , Prognóstico , Proteínas/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator Trefoil-1 , Proteínas Supressoras de Tumor
19.
Br J Cancer ; 88(5): 707-10, 2003 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-12618879

RESUMO

Adjuvant tamoxifen treatment reduces the occurrence of contralateral breast cancer (CBC). The aim of the study was to investigate the hypothesis that adjuvant tamoxifen reduces the occurrence of oestrogen-receptor (ER)-positive CBC, but not the growth of ER-negative CBCs, and to examine survival after diagnosis of CBC. For the study, ER status was immunohistochemically assessed in CBCs of 35 tamoxifen-treated patients and 115 patients without previous hormonal treatment. Cases were retrieved from a series of patients treated from 1984 to 1995 at nine hospitals. The interval between ipsi- and contralateral breast cancer was at least 1 year. It was seen that the proportion of patients with an ER-negative CBC was significantly higher among those with prior tamoxifen treatment: 37% vs 18% (P=0.047). No difference between the two groups in overall and disease-specific survival following CBC was found. However, the stage differed for both groups: tamoxifen users more often had node-positive contralateral disease (P= 0.045). In conclusion, metachronous CBCs developing after 1-3 years of tamoxifen treatment are more often ER-negative breast cancers. So far this does not seem to have a major impact on survival.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/tratamento farmacológico , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
20.
Ann Surg Oncol ; 9(10): 961-7, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12464587

RESUMO

BACKGROUND: Tumor markers are useful for diagnosis and follow-up. We studied the prognostic value of baseline and serial carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) measurements in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Sixty-three patients with pseudomyxoma peritonei were treated with cytoreductive surgery and HIPEC. The tumor markers CEA and CA19.9 were collected before therapy and at 3-month intervals during follow-up. RESULTS: Preoperative CEA and CA19.9 levels were increased in, respectively, 75% and 58% of the patients. Baseline tumor marker values were related to the extent of tumor. Immediately after HIPEC, both tumor markers decreased markedly (P <.0001). CA19.9 was shown to be a more useful tumor marker than CEA for follow-up. During follow-up, a high absolute CA19.9 level (P =.0005) was predictive for imminent recurrence. Patients who never attained a normal CA19.9 level showed a higher recurrence rate at 1 year (53%; SE, 15%), in comparison to patients who did so (6%; SE 4%). The median lead time of increased CA19.9 to recurrence was 9 months. CONCLUSIONS: The measurement of the tumor marker CA19.9 is useful in evaluating therapy in patients with pseudomyxoma peritonei treated with cytoreductive surgery and HIPEC. CA19.9 is a prognostic factor for predicting recurrent disease.


Assuntos
Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/metabolismo , Neoplasias Peritoneais/diagnóstico , Pseudomixoma Peritoneal/diagnóstico , Análise de Variância , Intervalo Livre de Doença , Humanos , Países Baixos/epidemiologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Pseudomixoma Peritoneal/mortalidade , Pseudomixoma Peritoneal/terapia , Recidiva , Taxa de Sobrevida
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