Patient-reported 'ever had' and 'current' long term physical symptoms following prostate cancer treatments

OBJECTIVE: To document prostate cancer patient reported 'ever experienced' and 'current' prevalence of disease specific physical symptoms stratified by primary treatment received.
PATIENTS: 3,348 prostate cancer survivors 2-15 years post diagnosis.
METHODS: Cross-sectional, postal survey of 6,559 survivors diagnosed 2-15 years ago with primary, invasive PCa (ICD10-C61) identified via national, population based cancer registries in Northern Ireland and Republic of Ireland. Questions included symptoms at diagnosis, primary treatments and physical symptoms (impotence/urinary incontinence/bowel problems/breast changes/loss of libido/hot flashes/fatigue) experienced 'ever' and at questionnaire completion ("current"). Symptom proportions were weighted by age, country and time since diagnosis. Bonferroni corrections were applied for multiple comparisons.
RESULTS: Adjusted response rate 54%; 75% reported at least one 'current' physical symptom ('ever':90%), with 29% reporting at least three. Prevalence varied by treatment; overall 57% reported current impotence; this was highest following radical prostatectomy (RP)76% followed by external beam radiotherapy with concurrent hormone therapy (HT); 64%. Urinary incontinence (overall 'current' 16%) was highest following RP ('current'28%, 'ever'70%). While 42% of brachytherapy patients reported no 'current' symptoms; 43% reported 'current' impotence and 8% 'current' incontinence. 'Current' hot flashes (41%), breast changes (18%) and fatigue (28%) were reported more often by patients on HT.
CONCLUSION: Symptoms following prostate cancer are common, often multiple, persist long-term and vary by treatment. They represent a significant health burden. An estimated 1.6% of men over 45 is a prostate cancer survivor currently experiencing an adverse physical symptom. Recognition and treatment of physical symptoms should be prioritised in patient follow-up. This information should facilitate men and clinicians when deciding about treatment as differences in survival between radical treatments is minimal.

Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial

Importance: The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.

Objective: To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients.

Design, Setting, and Participants: Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011.

Exposures: Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry.

Main Outcomes and Measures: Failure-free survival (FFS) and overall survival.

Results: A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).

Conclusions and Relevance: Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease.

Trial Registration: clinicaltrials.gov Identifier: NCT00268476; ISRCTN78818544.

Isoflavones in food supplements: chemical profile, label accordance and permeability study in Caco-2 cells

Consumers nowadays are playing an active role in their health-care. A special case is the increasing number of women, who are reluctant to use exogenous hormone therapy for the treatment of menopausal symptoms and are looking for complementary therapies. However, food supplements are not clearly regulated in Europe. The EFSA has only recently begun to address the issues of botanical safety and purity regulation, leading to a variability of content, standardization, dosage, and purity of available products. In this study, isoflavones (puerarin, daidzin, genistin, daidzein, glycitein, genistein, formononetin, prunetin, and biochanin A) from food supplements (n = 15) for menopausal symptoms relief are evaluated and compared with the labelled information. Only four supplements complied with the recommendations made by the EC on the tolerable thresholds. The intestinal bioavailability of these compounds was investigated using Caco-2 cells. The apparent permeability coefficients of the selected isoflavonoids across the Caco-2 cells were affected by the isoflavone concentration and product matrix.

Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies.

BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK.

Factores pronósticos de cáncer de seno: Hospital Militar Central enero 2003 a diciembre 2008

Introducción: el riesgo de desarrollar cáncer de seno durante la vida es del 13,4% (1 de cada 7 mujeres) y la posibilidad de morir por la enfermedad después del diagnostico es cercana al 30%. Pacientes y Métodos: es un estudio de cohorte abierta retrospectiva en el que se analizó la sobrevida según los factores pronósticos de las pacientes con cáncer de seno del hospital militar central en el periodo de enero de 2003 a diciembre de 2008. Los factores pronósticos son: Edad, estadío del tumor al momento del diagnóstico, Grado de diferenciación del tumor, presencia de metástasis al momento del diagnóstico, presencia de metástasis, número de sitios de metástasis, erb2, presencia de ganglios afectados, número de ganglios positivos, receptores estrogénicos, receptores de progestágeno, tratamiento con trastuzumab, tratamiento con hormonoterapia; el análisis estadístico se realizó a partir de la herramienta de recolección de datos, esta base de datos fue trasladada al programa SPSS. Resultados: participaron 171 mujeres. La presencia de receptores para estrógenos positivos se correlaciona con una mayor sobrevida con una diferencia estadísticamente significativa (p=0.015). Durante el periodo de tiempo del estudio fallecieron 23 pacientes (13.4%), de las cuales 20 (86%) presentaban Carcinoma Canalicular Infiltrante y 21 (91%) presentaban estadios avanzados del carcinoma. Conclusiones: las características demográficas de nuestra población son similares a lo publicado en la literatura, sin variantes estadísticamente significativas frente a los hallazgos internacionales. En nuestro análisis hubo una fuerte correlación de la presencia de estrógenos positivos en relación al tiempo de sobrevida.

Evaluación de disfunción sexual en pacientes sometidas a cabestrillo suburetral para corrección de incontinencia urinaria en el Hospital Universitario Mayor

Objetivo: establecer la prevalencia de la disfunción sexual en las pacientes sometidas a corrección de incontinencia urinaria por medio de la uretrocistopexia con cabestrillo en el Hospital Universitario Mayor. Metodología: se realizo un estudio analítico de corte transversal donde se evaluara la disfunción sexual en pacientes con incontinencia urinaria por medio de la encuesta PISQ-12 después de 6 meses de la realización de cabestrillo suburetral dentro del manejo de incontinencia urinaria femenina y buscarán la asociación con otros factores como el tipo de cirugía asociada al cabestrillo, menopausia, terapia hormonal, edad, número de embarazos utilizando la prueba de asociación ji-cuadrado de Pearson o el test exacto de Fisher o razón de verosimilitud exacta (valores esperados < 5). Resultados: la prevalencia de disfunción sexual fue del 27% (12 pacientes), de ellas 25% tuvieron disfunción moderada (11 pacientes) y dos por ciento disfunción severa (1 paciente) deacuerdo con la escala PISQ-12. La disfunción sexual fue más frecuente en las pacientes con prolapso posterior estadio 2 (4 de las 5 mujeres), seguido del prolapso anterior y posterior estadio 2 (4 de 10 mujeres), las otras categorías fueron menores, mostrando asociación significativa (p=0.011, Test exacto de Razón de verosimilitud). Conclusión: del presente estudio podemos concluir que la cirugía de piso pelvico (colporrafías) contomintante a la cirugía de incontinencia urinaria con cabestrillo suburetral está asociada a un mayor grado de disfunción sexual femenina.

Síndrome de turner: estudio de serie de casos de una población pediátrica en un hospital de Bogotá - Colombia (Fundación cardio-infantil agosto de 2003 - 2005)

Este es un estudio descriptivo, retrospectivo de reporte de serie de casos con Síndrome de Turner (ST), en el periodo comprendido Agosto 2003 a 2005 en un Hospital especializado de Nivel III de Bogotá Colombia. Se analizó las frecuencias de los cariotipos, fenotipos, de las malformaciones y ciertos procesos asociados, en una población de 31 pacientes con síndrome de Turner. Además, hemos estudiado la relación entre los cariotipos encontrados y los demás aspectos analizados.

Avaliação citológica em base líquida de fármacos moduladores estrogênicos

Hormone therapy is an important tool in the treatment of breast cancer and tamoxifen represents one of the most important drugs used in this type of treatment. Recently other drugs based on the inhibition of aromatase had been developed, this enzyme is responsible for the synthesis of estrogenic esteroids from the androgenic ones. The objective of this study would be the development of a quantitative cytological model of murine estral analysis that allowed the characterization of different hormone drugs effect over vaginal epithelium. The technique of monochromatic staining with Evans blue (C.I. 23860) showed to be efficient in the qualitative and quantitative classification of the cycle. It had been observed differences in the cytological standard of animals submitted to the studied drugs; tamoxifen presented a widening of phases of lesser maturation (diestrais), while anastrozole and exemestane increased the duration of the phases of larger maturation (estrais). The data were analysed through a cubical non linear regression (spline) which allowed a better characterization of the drugs, suggesting a proper cytological profile to the antagonism of the estrogen receptor (tamoxifen), aromatase competition (anastrozole) and inhibition of the enzyme (exemestane)

Fatores de risco para osteoporose em mulheres na pós-menopausa do sudeste brasileiro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Indicadores antropométricos e as doenças crônicas não transmissíveis em mulheres na pós-menopausa da região Sudeste do Brasil

OBJETIVO: avaliar a influência dos indicadores antropométricos sobre os marcadores de risco cardiovascular e metabólico para doenças crônicas não-transmissíveis em mulheres na pós-menopausa. MÉTODOS: realizou-se estudo clínico transversal, com 120 mulheres sedentárias na pós-menopausa (com idades entre 45 e 70 anos e última menstruação há, pelo menos, 12 meses). Foram excluídas as diabéticas insulino-dependentes e usuárias de estatinas ou terapia hormonal até seis meses prévios. Para avaliação antropométrica, foram obtidos peso, estatura, índice de massa corpórea (IMC=peso/altura²) e circunferência da cintura (CC). As variáveis metabólicas avaliadas foram colesterol total (CT), HDL, LDL, triglicérides (TG), glicemia e insulina, para os cálculos do índice aterogênico plasmático (IAP) e resistência insulínica (Homeostasis model assessment-insulin resistance, HOMA-IR). Na análise estatística, utilizara-se análise de variância one-way (ANOVA) e Odds Ratio (OR). RESULTADOS: os dados médios caracterizaram amostra com sobrepeso, com obesidade central e dislipidêmica. Sobrepeso e obesidade estiveram presentes em 77,1% e deposição central de gordura ocorreu em 87,3% das participantes. Os valores médios de CT, LDL e TG estavam acima do recomendável em 67,8, 55,9 e 45,8% das mulheres, respectivamente, com HDL abaixo dos valores adequados em 40,7%. Valores de CC >88 cm ocorreram em 14,8% das mulheres eutróficas, 62,5% no grupo com sobrepeso e 100% nas obesas (p>0,05). Os valores médios de IAP, TG e HOMA-IR aumentaram significativamente com o aumento do IMC e da CC, enquanto que o HDL diminuiu (p<0,05). Na presença da CC >88 cm, encontrou-se risco de 5,8 (IC95%=2,3-14,8), 2,61 (IC95%=1,2-5,78), 3,4 (IC95%=1,2-9,7) e 3,6 (IC95%=1,3-10,3) para HDL reduzido, hipertrigliceridemia, IAP elevado e resistência a insulina, respectivamente (p<0,05). O IMC >30 kg/m² associou-se apenas com HDL reduzido (OR=3,1; IC95%=1,44-6,85). CONCLUSÕES: a associação de duas medidas antropométricas (CC e IMC) foi eficiente para adequado diagnóstico de obesidade relacionada a alterações metabólicas em mulheres na pós-menopausa. Contudo, a simples avaliação da CC pode ser indicativo do risco cardiovascular e metabólico das doenças crônicas não transmissíveis.

Effect of raloxifene on the vaginal epithelium of postmenopausal women

Objective: The objective was to analyze the effect of raloxifene oil the vaginal epithelium of postmenopausal women.Study design: In this non-randomized clinical trial, 80 women (mean age = 60.6 years) were prospectively studied. Forty patients received 60 mg/day of raloxifene (RG), and 40 women constituted it non-treated control group (CG), paired by age and time since menopause. The treated group consisted of patients with osteoporosis of the lumbar spine. Those with a diagnosis of infection ill the lower genital tract and using hormone therapy (HT) up to 6 months prior to the study were excluded. Vaginal smears were collected at baseline and after 6 months of intervention. The vaginal maturation value (VMV) was determined, and counts of superficial, intermediate and parabasal cells were performed. Smears were analyzed by only one cytopathologist who was blinded to patient data. The t-test, Wilcoxon test, and Chi-Squared test were used in the statistical analysis.Results: The study groups were homogeneous regarding age, time since menopause, parity, HT use, smoking, and body mass index. No statistically significant differences were observed in VMV median values (RG, 39.7 and 35.7; CG, 50.0 and 50.0, respectively) or in the percentage of superficial, intermediate and parabasal cells between the groups at baseline and after 6 months (p > 0.05). There was no significant correlation between VMV and age, time since menopause, previous HT use, or body mass index, in either of the groups.Conclusion: Treatment with raloxifene for 6 months has no effect on the maturation of the vaginal epithelium ill postmenopausal women with osteoporosis. (C) 2008 Elsevier B.V. All rights reserved.

Assessment of risk factors for low bone mineral density in Brazilian postmenopausal women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metabolic syndrome and its associated risk factors in Brazilian postmenopausal women

Objective To evaluate the prevalence of metabolic syndrome (MetS) and its associated risk factors in Brazilian postmenopausal women.Methods In this cross-sectional study, a total of 368 postmenopausal women, aged 40-75 years, seeking health care at a public outpatient center in Southeastern Brazil, were included. According to the US National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, MetS was diagnosed in subjects with three or more of the following: waist circumference >= 88 cm, blood pressure >= 130/85 mHg, triglycerides >= 150 mg/dl, high density lipoprotein cholesterol <50 mg/dl and glucose >= 110 mg/dl. Data on past medical history, tobacco use, anthropometric indicators, and values of C-reactive protein (CRP) were collected. Multivariate analysis, using a logistic regression model (odds ratio, OR) was used to evaluate the influence of various simultaneous MetS risk factors.Results The prevalence of having at least three, four and five MetS diagnostic criteria were met in 39.6%, 16.8% and 3.8% of the cases, respectively. The most prevalent risk factor was abdominal obesity, affecting 62.5% of women. The risk of MetS increased with a personal history of diabetes (OR 5.95, 95% confidence interval (CI) 2.82-12.54), hypertension (OR 4.52, 95% CI 2.89-7.08), cardiovascular disease (OR 2.16, 95% CI 1.18-3.94) and high CRP (>1 mg/dl) (OR 3.35, 95% CI 1.65-6.79). Plasma CRP levels increased with the number of MetS components present. Age, time since menopause and smoking had no influence, while hormone therapy reduced MetS risk (OR 0.64, 95% CI 0.42-0.97).Conclusion Metabolic syndrome was highly prevalent among Brazilian postmenopausal women seeking gynecologic health care. Abdominal obesity, diabetes, hypertension and high CRP were strong MetS predictors and hormone therapy appeared to play a protective role for this condition.

Quality of life in women with vulvar cancer submitted to surgical treatment: a comparative study

Objectives: To investigate the occurrence and severity of lymphoedema of the lower extremities (LLE), quality of life (QoL), and urinary and sexual dysfunction in women with vulvar cancer submitted to surgical treatment.Study design: Twenty-eight patients with vulvar cancer submitted to vulvectomy and inguinofemoral lymphadenectomy and 28 healthy, age-matched women (control group) were evaluated. The occurrence and severity of LLE were determined by Miller's Clinical Evaluation. QoL, urinary function and sexual function were assessed by the EORTC QLQ-C30, SF-ICIQ and FSFI questionnaires, respectively. The differences between groups and correlations were assessed using Student's r-test, Chi-squared test, Mann-Whitney U-test and Spearman's rho test.Results: The groups were similar in terms of marital status, educational status, menopausal status, hormone therapy and height. The occurrence and severity of LLE were higher in women with vulvar cancer compared with the control group (p < 0.001 and p = 0.003, respectively). A significant association was found between the severity of LLE and advanced age (p = 0.04), and the severity of LLE and higher body mass index (BMI; p = 0.04) in patients with vulvar cancer. In the patients with vulvar cancer, there was a significant correlation between the severity of LLE and worse QoL in the following domains: physical, cognitive, emotional, social, fatigue, pain, sleep and financial questions (p < 0.05). There was no difference in urinary function between the two groups (p = 0.113). Age and number of deliveries were the only variables associated with the occurrence of urinary incontinence (p = 0.01). Urinary incontinence was present in women with a mean age of 74.9 +/- 4.6 years and a mean of 7.3 +/- 1.3 normal deliveries. There was no difference between the groups in terms of the sexual function. Multivariate analysis showed an association between sexual function and age (p = 0.01), and sexual function and being in a stable relationship (p = 0.02).Conclusion: Patients submitted to vulvectomy or inguinofemoral lymphadenectomy for vulvar cancer are at higher risk of developing LLE compared with healthy, age-matched women. This has a negative effect on QoL, but does not interfere with urinary or sexual function. (C) 2012 Elsevier B.V. All rights reserved.