CO2 vaginal laser alone or in combination with topical estriol is a good treatment option for VVA symptoms. Sexual-related pain with vaginal laser treatment might be of concern.

Our aim was to retrospectively evaluate the influence of gemistocytic astrocytes, cellular proliferation indices, immunoexpression of proteins p53 and bcl-2 in the clinical outcome of 39 patients with WHO grade II and III astrocytomas with the presence of gemistocytes. The mean proportion of gemistocytes was 18.7% and the mean proliferative index was 3.3%. Immunoexpression of p53 was detected in 29 cases (74.4%) and all cases (100%) were positive for bcl-2. The median overall survival was 97.2 months and the progression-free survival was 43.1 months. Estimated 1-, 5- and 10-year overall survival rates were 94.3%, 69.5% and 46.4%; 1-, 5- and 10-year progression-free survival rates were 91.1%, 26.1% and 13.1%. Out of 24 who presented clinical and neuroimaging worsening, characterized as tumor progression or recurrence, 16 had histological confirmation and were also analyzed. We could not detect significant differences when comparing all the indices between WHO grade II and III and also between the first and second biopsies. We also could not detect significant differences in progression-free and overall survival when analyzing the gemistocyte index and the immunohistochemical labeling indices p53, bcl-2 and MIB-1, as well as patientsa9 age (median value, up to 34 vs. over 34 years) and histological grade (II or III). Our finding confirms recent reports that question the role of gemistocytes as a prognostic factor in diffuse astrocytomas. The significance and role of gemistocytes in astrocytomas has yet to be defined and warrants further study.

Giant prostatic hyperplasia is a rare condition characterized by very high volume benign prostatic enlargement (>500g). Few cases have been reported so far and most of them are associated with severe lower urinary symptoms. We report the first case of asymptomatic giant prostatic hyperplasia in an elderly man who had a 720g prostate adenoma, sudden gross hematuria and hypovolemic shock. The patient was successfully treated with open transvesical prostatectomy and had an uneventful postoperative recovery.

Context:Polyacrylate-polyalcohol copolymer is a synthetic product, non-biodegradable, with low rate of therapeutic failure and lower incidence of reactions at the site of injection, when compared to biodegradable agents. We report an unprecedent, exuberant and persistent inflammatory reaction following injection of that substance.Patient:a 17 years-old patient with vesico-ureteral reflux and complete pyelocaliceal right duplication was submitted to treatment with polyacrylate-polyalcohol copolymer (STING technique). In the seventh day of post-operatory, she presented intense dysuria and hypogastric pain, without laboratory exams alterations; a symptomatic treatment was started. After two months, the symptoms persisted and an ultrasound detected thickening of bladder wall close to the uretero-vesical junction. After that exam, a cystostopic biopsy showed epithelial hyperplasia with increased edema of lamina propria, suggesting an adverse reaction to the polymer. After four months, there was complete remission, but the reflux persisted with the same grade.Hypothesis:This is an unprecedent reaction following injection of this copolymer. The presence of characteristics such as absence of infection, temporal relation between treatment and beginning of symptoms, and detection of epithelial hyperplasia at the local of injection reinforce the hypothesis of association of the substance and adverse reaction. In that patient, important complains motivated early investigation of urinary tract, that confirmed those aspects. Maybe if that reaction had occurred in patients with lower capacity of expression (such as in infants) it would be unnoticed.

During initial risk assessments, the metastatic potential of prostate cancer (PCa) may not be fully considered. The tumor's multicentric origin, which is associated with genetic mutations, may explain existing treatment limitations. Investigating human epidermal growth factor receptor 2 (HER2) expression in patients with different stages of PCa may therefore increase understanding of the mechanisms associated with the development of castration resistance. The present study examined the association between HER2 expression and the histologic features of PCa subjected to radical prostatectomy (RP) and evaluated the role of testosterone suppression in HER2 expression. In group 1, specimens from individuals who underwent RP without prior neoadjuvant androgen deprivation therapy (ADT) were included (n=42). In group 2 (PCa with ADT), specimens from individuals who underwent RP and received neoadjuvant cyproterone acetate during distinct periods (200 mg daily for 1-24 months) were included (n=150; cohort derived from a previous study). Immunohistochemical expression of HER2 was associated with prognostic factors such as perineural invasion, extra-prostatic disease, T stage, serum prostate-specific antigen (PSA), angiolymphatic invasion and surgical margins. Univariate regression analysis indicated that perineural invasion, PSA, International Society of Urological Pathology, angiolymphatic invasion, margin, T stage and neoadjuvant ADT was associated with HER2 expression. Ordinal regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (P<0.001). In addition, regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (odd ratio=0.01; 95% CI, 0.00, 0.02; P<0.001). HER2 was expressed in PCa samples but was not associated with known prognostic factors. The use of short-acting ADT and the consequent blockage of testosterone effect may suppress the expression of HER2 in PCa cells.

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RESUMO -Foram estudados, retrospectivamente, 22 pacientes com diagnóstico de astrocitomas grau II (n=17) e III (n=5), OMS, no período de 1990 a 1998, cujos laudos histopatológicos descreviam a presença gemistocitos com o objetivo de determinar o índice de astrócitos gemistocíticos, investigar a imuno-expressão da proteína p53 e confrontá-los com o intervalo até a recorrência da neoplasia. O índice de astrócitos gemistocíticos, em cada caso, foi calculado a partir da razão entre o número de gemistocitos e o número total de células neoplásicas contadas, no mínimo 1000. Imuno-expressão nuclear da proteína p53 foi avaliada em astrócitos e gemistocitos neoplásicos; tanto a freqüência (7/22), como o índice de imuno-expressão positiva da p53 em gemistocitos, independentemente do grau histológico da neoplasia, foram inferiores aos relatados na literatura. Não se observou correlação entre o índice de astrócitos gemistocíticos e a imuno-expressão positiva da p53.PALAVRAS-CHAVE: gemistocito, p53, astrocitoma, glioma. Fraction of gemistocytic astrocytes and immunoexpression of p53 protein in astrocytomas grade II and III (WHO)ABSCTRACT -Twenty-two patients with astrocytomas, grade II or III WHO, were studied from 1990 to 1998. In all cases, histopathology showed that the astrocytomas had a gemistocytic component. The aims of this study were to establish the fraction of gemistocytic astrocytes, to investigate p53 protein immunoexpression and to evaluate correlations between these two parameters with the tumour outcome. Tumor cells were quantified at high-power magnification (x400). At least 1000 neoplastic cells (small neoplastic astrocytes plus gemistocytes) were counted in each specimen. The percentage of gemistocytes was defined as the gemistocytic index. Nuclear expression of p53 protein was evaluated in neoplastic astrocytes and gemistocytes. Both the frequency (7/22) as well the p53 immunoexpression indices in gemistocytes, regardless of the grade of the astrocytomas, were inferior from those reported in the literature. No correlation was found between the gemistocytic indices and the p53 immunoexpression.KEY WORDS: gemistocytes, p53, astrocytoma, glioma. Astrocitomas difusos abrangem grande espectro de neoplasias desde lesões que crescem lentamente, até tumores altamente agressivos e fatais. Uma característica importante desse grupo de neoplasias é a tendência à recorrência, frequentemente acompanhada da progressão para fenótipos mais malignos, o que é um aspecto particular dos astrocitomas gemistocíticos. Gemistocitos não são observados no tecido cerebral normal ou durante a embriogênese 1-3 . Entretanto, sua presença em neoplasias tem sido considerada um fator de pior prognóstico 4 . Vários estudos têm mostrado que a evolução dos astrocitomas para graus maiores de anaplasia, reflete aquisição seqüencial de alterações genéticas [5][6][7] . Como nos astrocitomas de baixo grau, mutações no gene p53 são as alterações genéticas mais comuns e estão presentes em freqüências semelhantes nos astrocitomas anaplásicos e gliobl...

BackgroundAnifrolumab is a fully human anti–interferon-α receptor monoclonal antibody in Phase III development for systemic lupus erythematosus (SLE). In Phase IIb trials, intravenous (IV) anifrolumab (300 mg every 4 weeks) significantly decreased SLE disease activity with safety and tolerability comparable to placebo.1ObjectivesThe primary objective of this Phase I, double-blind, randomized, controlled study (NCT02601625) was to characterize the pharmacokinetics (PK), safety, and tolerability of anifrolumab administered subcutaneously (SC) and intravenously to healthy volunteers.MethodsThirty male and female adults were assigned to three sequential treatment cohorts of equal size (anifrolumab 300 mg SC injection; anifrolumab 300 mg IV; anifrolumab 600 mg SC by infusion). Individuals were randomized within each cohort to receive a single dose of either anifrolumab (n=6/cohort) or placebo (PBO) (n=4/cohort). Serial blood samples were collected up to Day 85. Serum anifrolumab concentrations were analyzed with a validated assay. PK parameters were estimated by noncompartmental analysis. Immunogenicity of anifrolumab was assessed by measuring serum anti-drug antibodies (ADAs).ResultsAnifrolumab serum concentration-time profiles and primary PK parameters in healthy volunteers are presented in the figure and table, respectively. Anifrolumab serum concentrations were below the limit of detection in all individuals by 85 days post dose. Maximum serum concentrations in the SC cohorts occurred after 4 to 7 days. Exposure to SC anifrolumab increased approximately dose proportionally from 300 mg to 600 mg based on AUC. At the 300-mg dose, anifrolumab exposure after SC administration reached approximately 86% of the IV administration exposure. SC administration of anifrolumab 300 mg and PBO elicited minimal injection-site reactions. Transient injection-site induration occurred in five of six individuals in the anifrolumab 600-mg group and two of four in the PBO group. Transient, mild to moderate injection-site induration and pruritus occurred simultaneously in two of six individuals in the anifrolumab 600-mg group, but not those in the PBO group. Adverse events were reported by 50% (n=9) of anifrolumab-treated and 33% (n=4) of PBO-treated individuals. No serious adverse events were observed. ADAs were detected in only one individual in the anifrolumab 300-mg IV group at the Day-85 assessment.Anifrolumab Serum PK ParametersAnifrolumab 300 mg SC (N=6)300 mg IV (N=6)600 mg SC (N=6) Cmax (μg/mL) Mean ± SD36.2±11.682.4±13.263.9±20.5 CV (%)32.116.032.0AUC (day.μg/mL) Mean ± SD785±331907±1751,828±680a CV (%)42.119.337.2tmax (day) Median4.130.037.00 Minimum–maximum4.02–7.000.03?1.033.96?8.95aN=5 because 1 individual was lost to follow-up at 1 month post dose. AUC = area under serum concentration-time curve from time zero extrapolated to infinity; Cmax = observed maximum serum concentration; CV = coefficient of variation; tmax = time to reach maximum serum concentration.ConclusionsExposure of anifrolumab 300 mg SC was approximately 8...