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Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.
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BACKGROUND: Bone metastases (BMs) are associated with significant morbidity and shorter survival in renal cell carcinoma (RCC). Our purpose was to identify prognostic factors for overall survival (OS) in RCC patients with BMs. METHODS: Data from patients with BMs from RCC treated at Gustave Roussy between April 1992 and March 2016 were retrospectively collected. Age, sex, Eastern Cooperative Oncology Group-Performance Status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk groups, histology, number and site of bone lesions, concomitant metastases (presence and sites), therapy for BMs (radical resection or palliative surgery, radiotherapy and other local and systemic treatments) and time from diagnosis to BMs were analysed. Synchronous solitary bone metastasis (SSBM) was defined as a single BM without concomitant visceral lesions at the initial diagnosis of RCC. OS was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Maier method and modelled with Cox regression analysis. RESULTS: From 1750 patients with diagnosis of RCC followed at Gustave Roussy Cancer Campus, 300 patients with BMs were identified. Median time from diagnosis to BMs was 32.4 months (range 0-324 months). In 64 patients (21%), bone was the only metastatic site, and 22 patients (7%) had an SSBM and 236 patients (79%) had concomitant metastases in other sites. Median OS was 23.2 months (95% confidence interval 19.9-26.2). SSBM patients had better OS than those with concomitant metastases (40 vs 20 months; P < 0.001). At multivariate analysis, concomitant metastases remained predictor of poor prognosis, while MSKCC risk group, radical resection and SSBM were predictors of better OS. CONCLUSIONS: This study suggests that MSKCC score, numbers of BMs and radical resection are important prognostic factors for RCC patients with BMs. Additionally, in the presence of solitary BM without concomitant metastases at the initial diagnosis of RCC, bone surgery should be considered to achieve local tumour control and likely increase OS.
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Neoplasias Ósseas/secundário , Institutos de Câncer/estatística & dados numéricos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/terapia , Carcinoma de Células Renais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. PATIENTS AND METHODS: PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged <75 years was pre-specified for the coprimary end points and adverse events (AEs). RESULTS: Among 609 elderly patients (35%) who participated in PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide and placebo arms, respectively. In the elderly subgroup, OS was greater with enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs was similar between the two age groups, except for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. CONCLUSIONS: Elderly men benefited from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide treatment were associated with a higher incidence of falls. CLINICAL TRIAL IDENTIFIER: NCT01212991, ClinicalTrials.gov.
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Antagonistas de Receptores de Andrógenos/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acidentes por Quedas/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Andrógenos/efeitos adversos , Antineoplásicos/efeitos adversos , Benzamidas , Intervalo Livre de Doença , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Placebos , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
Androgen deprivation therapy is the mainstay of treatment for men affected by metastatic prostate cancer (PC). Unfortunately, nearly all patient will become resistant to the initial hormonal approach, developing a metastatic castration-resistant prostate cancer (mCRPC). For many years, chemotherapy with docetaxel has been the only established standard of care for men with mCRPC. Recent developments in the knowledge of the disease biology have shown that during the progression to the castrate status PC remains dependent on androgens and androgen receptor (AR) pathway. As a consequence, new agents like abiraterone acetate and enzalutamide have been rapidly developed and approved for clinical use. Other drugs with different mechanisms of action, such as sipuleucel-T, cabazitaxel, and radium-223 have shown to improve overall survival, symptom control and quality of life of mCRPC patients. However, the optimal sequencing and combination of these treatments are not defined yet. Studies on biomarkers for treatment selection, such as AR splice variants, are promising, but the initial data still need prospective validation on large patient series.
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Antineoplásicos/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Animais , Antineoplásicos/uso terapêutico , Humanos , Imunoterapia , Masculino , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/imunologia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Análise de SobrevidaRESUMO
BACKGROUND: Through different pharmacodynamic-kinetic interactions, weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit. Based on this assumption, we designed a phase I-II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients. PATIENTS AND METHODS: We enrolled 56 previously untreated metastatic breast cancer patients; they were randomly assigned to receive paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4 weeks. The primary end points were the clinical benefit and treatment-related toxic effects assessment. Secondary end points were time-to-disease progression (TTP) and overall survival (OS). RESULTS: The overall clinical benefit was 87.04%. World Health Organization G3-4 toxic effects included neutropenia (45%), anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24% of patients developed left ventricular ejection fraction reduction but none >10% with recover after treatment completion. The median absolute decrease from baseline was 1%. Median TTP was 11 months and median OS was 23 months. CONCLUSIONS: Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Taxoides/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Doxorrubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Taxoides/administração & dosagemRESUMO
We studied a group of 18 patients with mitral valve prolapse (MVP) and a group of 20 healthy controls. Subjects in both groups were subjected to a 1-h experimental stress exposure during which Holter-ECG monitoring was performed and was then continued for the following 24 h. MVP patients complained of significant cardiac palpitation during the stress session, but ECG examination did not reveal significant inter-group differences. However, the two groups did show statistically significant differences in some psychometric measurements (Toronto Alexithymia Scale, Anxiety Sensitivity Index, Fear Questionnaire, Beck Depression Inventory, and Harm Avoidance subscale of Tridimensional Personality Questionnaire) that underlie personality traits known to be important in the process fostering functional somatic symptoms, according to the somatosensory amplification model. As no objective signs of cardiac rhythm modification were found in MVP patients under stress, we postulate that the symptoms for which these patients were referred have a functional nature, and that there is no pathogenetic link with the underlying valvular defect.
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Prolapso da Valva Mitral/fisiopatologia , Estresse Psicológico/fisiopatologia , Adulto , Eletrocardiografia , Feminino , Humanos , Masculino , PsicometriaRESUMO
High resolution P-waves of 28 patients having a mean age of 45 years and affected by isolated mitral valve stenosis (nine of whom showed paroxysmal atrial fibrillation) have been compared with those obtained from 30 healthy subjects about 35 years old. Our primary aim was to characterize the signal-averaged P-wave in mitral valve stenosis. Parameters which differed between the two groups in time domain analysis were the P-wave duration, the abscissa of the maximum positive voltage amplitude, the peak-to-peak amplitude and the integrated voltage-time product, which turned out to be greater in the patient class than in the healthy set; furthermore, in the frequency domain analysis, amplitudes in the range from 37 to 60 Hz were greater in healthy subjects than in patients. A successive analysis carried out to predict those patients with mitral valve stenosis who are at risk of developing paroxysmal atrial fibrillation showed that the P-wave duration and the amplitudes (in the range 60-106 Hz) were the most distinctive parameters, but, unfortunately, without any significant difference with respect to those of patients with mitral valve stenosis alone. Finally, some correlations between the age, the P-wave duration and the left atrial diameter of patients, were revealed to exist only in patients affected by episodes of atrial fibrillation.
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Fibrilação Atrial/diagnóstico , Função Atrial , Eletrocardiografia/métodos , Estenose da Valva Mitral/diagnóstico , Processamento de Sinais Assistido por Computador , Adulto , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Feminino , Análise de Fourier , Humanos , Pessoa de Meia-Idade , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: Patients with ischemic heart disease and episodes of paroxysmal atrial fibrillation are at major risk of stroke. In order to prevent such episodes, through the identification of patients prone to atrial fibrillation, we investigated the high-resolution atriogram of 65 patients with chronic ischemic heart disease, 54 male and 11 female, mean age 60.22 +/- 9.04 years. Based on previous documented episodes of atrial fibrillation, the patients were divided into two groups: group A, 45 males and 3 females, mean age 58.92 +/- 7.68 years, without atrial fibrillation; group B, 9 males and 8 females, mean age 63.88 +/- 11.6 years, with atrial fibrillation. RESULTS: High resolution atrial duration (100-300 Hz) in group B (with atrial fibrillation) was higher than in group A (without atrial fibrillation) (140.59 +/- 16.85 ms vs 121.77 +/- 11.27 ms, p < 0.001); Non filtered atrial duration (0-300 Hz) was not different between the two groups, A and B (118.54 +/- 10.96 ms vs 123.53 +/- 18.77 ms, p = NS); The prevalence of late atrial potentials was higher in group B than in group A (60.8% vs 7.1%, p < 0.001); No relation was observed between high resolution atriogram data and echocardiographic measurements; Sensibility was 82%, specificity 81%, and predictivity 60%. CONCLUSIONS: Data from our study show that high resolution electrocardiography is a valid tool for identifying patients prone to atrial fibrillation. Such patients can be identified by the presence of "late atrial potentials" that, like late ventricular potentials for ventricular tachycardia, are correlated with atrial fibrillation. Nevertheless, a larger cohort of patients is necessary to confirm these results.
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Fibrilação Atrial/etiologia , Isquemia Miocárdica/complicações , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Doença Crônica , Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , Eletrocardiografia Ambulatorial , Feminino , Átrios do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologiaRESUMO
BACKGROUND: Patients with hypertrophic cardiomyopathy are at increased risk of sudden death. Recently it has been investigated whether late potentials can be useful markers of that risk in such patients, with discordant results. The aim of our study was to detect a correlation, if any, between late potentials, ventricular tachycardia and the hypertrophy extension. METHODS: Twenty-five patients were enrolled, 19 males and 6 females, mean age 40.40 +/- 15.02 years. Each underwent 24h Holter monitoring, averaged ECG, M-Mode and 2-D Echo. The hypertrophy was considered extensive (septum and free wall) or non extensive (septum and/or apex). RESULTS: Late potentials of a mean duration of 37 +/- 14.83 ms were recorded in 5/7 patients with documented ventricular tachycardia vs in none of the non tachycardia group. Sensibility was 100%, specificity 71% and predictive value 100%. Late potentials were present in 8.3% of patients with non extensive and in 30.8% of patients with extensive hypertrophy (p = NS). CONCLUSIONS: From our data it seems that extensive hypertrophy is present in about half of patients with hypertrophic cardiomyopathy, and this roughly correlates with a more frequent ventricular tachycardia and with late potentials. Furthermore, late potentials are strictly related to the incidence of ventricular tachycardia in this disease, just as in ischemic heart disease or in idiopathic dilated cardiomyopathy. The small number of our cases may not be sufficient to reach a significant statistical correlation between late potentials and hypertrophy, but we believe that the trend is very promising.
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Cardiomegalia/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Potenciais de Ação , Adolescente , Adulto , Idoso , Cardiomegalia/complicações , Cardiomegalia/diagnóstico por imagem , Criança , Eletrocardiografia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Taquicardia Ventricular/etiologia , UltrassonografiaRESUMO
Twenty-five patients with idiopathic dilated cardiomiopathy were investigated in order to evaluate the role of late ventricular potentials as possible markers of ventricular tachycardia or sudden cardiac death. Holter monitoring showed ventricular tachycardia in 9 patients (group A) all of whom had late ventricular potentials, (mean +/- SD length 37.22 +/- 15.83 ms and mean +/- SD voltage 5.62 +/- 2.78 microV). Mean +/- SD ejection fraction in this group was 20 +/- 9.39%. In 16 patients (group B), without ventricular tachycardia, means +/- SD ejection fraction 27.5 +/- 8.17%; late ventricular potentials were recorded in 2 patients. During the follow-up period (means +/- SD 11.53 +/- 7.19 months), 3 patients underwent heart transplantation, 2 patients underwent pace-maker implantation and 2 patients from the ventricular tachycardia group died one from sudden cardiac death and the other from progressive heart failure. No significant differences were found in the ejection fraction either between the ventricular tachycardia and the non-ventricular tachycardia group, or between the late ventricular potentials and the non-late ventricular potential groups. Negative data were also obtained when we tried to find a correlation between the ejection fraction and late ventricular potential length and/or voltage. Good results were observed with regard to sensitivity (100%), specificity (87%) and predictive accuracy (81%) but follow-up data did not specify a definite prognostic value for late ventricular potentials. The Authors conclude that late ventricular potentials are markers of patients with idiopathic dilated cardiomyopathy who are prone to ventricular tachycardia. However, the role of late ventricular potentials in sudden cardiac death is still uncertain.
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Cardiomiopatia Dilatada/fisiopatologia , Adolescente , Adulto , Idoso , Cardiomiopatia Dilatada/tratamento farmacológico , Criança , Morte Súbita , Eletrocardiografia , Feminino , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia/fisiopatologiaRESUMO
Detailed QRS wave analysis from the limb leads of the surface high resolution electrocardiograms recorded in five cyclosporine-treated heart transplant recipients gave good correlation with the corresponding results of endomyocardial biopsy. That is when the result of the biopsies has identified the presence of rejection, a concomitant (p = 0.001) variation in some parameters of the QRS has been observed. The reproducibility of such parameters (established by means of the correlation coefficient r) gave r values ranging from 0.6 up to 0.93. The correlation regarded parameters analyzed both in time and frequency domain. Biopsy results were divided into two classes on the basis of the presence or absence of rejection. The most significant parameters obtained from high-frequency (25-300 Hz) ECGs within a few hours of each biopsy were: a) the total high-frequency voltage amplitude Vt of the QRS and the voltage amplitude of its initial Vi and middle thirds Vm; b) the peak voltage amplitude Vp of the QRS; c) the QRS duration L; d) the integrated voltage time product I of the QRS; e) three mean voltage amplitudes V5, V6, V7, of the power spectral density constructed on the basis of the 512-point fast Fourier transform applied on each recording. The above mentioned parameters appear to be useful in predicting the biopsy result in terms of the presence or absence of rejection.
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Eletrocardiografia/métodos , Rejeição de Enxerto , Transplante de Coração , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Ciclosporinas/uso terapêutico , Endocárdio/patologia , Feminino , Análise de Fourier , Rejeição de Enxerto/efeitos dos fármacos , Coração/fisiopatologia , Transplante de Coração/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The findings of a study carried out on a sample of 403 P waves, selected over the 50 to 300 Hz frequency range, by a portable microcomputer system capable of averaging 512 P waves, are reported. Detailed analysis of P waves was attempted in healthy subjects and in patients affected by pathologic processes where atrial involvement had been observed. An attempt was made to individualize P wave parameters which may be associated with these pathologic conditions. On each atrial signal a 512-point fast Fourier transform was used. The original sample was divided into 18 classes, and the mean values of some parameters of each class were computed. The results of fast Fourier transform computing and of the mean values of parameters for both patients and healthy subjects show two different behaviors with respect to the amplitude-frequency relationships and mean peak-to-peak amplitude, respectively. The present results indicate that this technique may be useful for further detailed analysis of P waves.
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Eletrocardiografia , Adulto , Doença das Coronárias/fisiopatologia , Feminino , Análise de Fourier , Átrios do Coração/fisiopatologia , Humanos , Masculino , Microcomputadores , Pessoa de Meia-Idade , SoftwareAssuntos
Hipertensão/genética , Eletrocardiografia , Teste de Esforço , Feminino , Hemodinâmica , Humanos , Masculino , RiscoRESUMO
High resolution tracings of atrial depolarization can be obtained by surface signal averaging technique. A study was conducted on 4 male and 4 female healthy MZ twin pairs aged 10.4 +/- 1.3 yrs. Each subject underwent 3 or more recordings, at 10-days intervals. The essential reproducibility could be confirmed, with personal characteristics, as well as the reliability of the technique and the electrophysiological value of the spikes complex. In 3/8 pairs the cotwins showed a significant likeness of the atriogram, while in 5/8 pairs the tracings were not quite resembling between the twins and that is attributed to variations in the chronogenetic characteristics of MZ twins.