The presence of extracapsular extension is associated with an increased risk of death from prostate cancer after radical prostatectomy for patients with seminal vesicle invasion and negative lymph nodes

ObjectivesDetermining clinicopathologic features that stratify the risk of disease progression in patients with seminal vesicle invasion at radical prostatectomy remains critical for patient counseling, clinical trial enrollment, and the judicious application of secondary therapies. Then, we evaluated the prognostic significance of concomitant extracapsular extension (ECE) in patients with seminal vesicle invasion and negative lymph nodes at radical prostatectomy.MethodsWe identified 1,132 patients who underwent prostatectomy between 1987 and 2009 and were found to have pT3bN0 disease. Median postoperative follow-up was 10.6 years (interquartile range, 5.9–15.3). Survival was estimated using the Kaplan-Meier method and compared for patients with and without ECE with the log-rank test. The association of ECE with outcome was evaluated using Cox proportional hazards regression models.ResultsA total of 693 (61%) patients were noted to have ECE. Compared with pT3bN0 patients without ECE, patients with pT3bN0 tumors and ECE had a significantly worse 15-year biochemical recurrence-free survival (29% vs. 39%; P<0.001), systemic progression-free survival (71% vs. 81%; P<0.001), cancer-specific survival (80% vs. 89%; P<0.001), and overall survival (50% vs. 63%; P<0.001). On multivariate analysis, the presence of ECE was associated with significantly increased risks of systemic progression (hazard ratio [HR], 1.56; P=0.006), death from prostate cancer (HR, 1.71; P=0.01), and all-cause mortality (HR, 1.35; P=0.007). Meanwhile, adjuvant hormonal therapy, which was received by 334 patients (29.5%), was associated with significantly decreased risks of systemic progression (HR, 0.50; P=0.0004) and cancer death (HR, 0.57; P=0.03), but not all-cause mortality (HR, 0.81; P=0.09). Limitations included retrospective design and nonstandardized application of secondary treatments.ConclusionsThe presence of ECE in patients with pT3bN0 prostate cancer is associated with increased risks of systemic progression and cancer death. Pending validation, ECE may be incorporated into risk stratification or staging classification or both. Meanwhile, these patients continue to represent ideal candidates for adjuvant therapy trials.     

Availability of ulipristal acetate: A secret shopper survey of pharmacies in a metropolitan area on emergency contraception

ObjectivesTo assess levonorgestrel (LNG) and ulipristal acetate (UPA) availability in pharmacies in a metropolitan area.MethodsA cross-sectional survey was conducted of all identified pharmacies within 25 miles of an urban medical center in Kansas City, KS. We categorized the pharmacies as dedicated commercial (national chains), store-associated (affiliated with a general merchandise or grocery store), or independent. We assessed LNG and UPA availability or time to availability if not currently stocked.ResultsWe contacted 165 pharmacies. Of the 165 pharmacies, few stocked UPA (12/165, 7%) whereas the majority stocked oral LNG (128/165, 78%). Dedicated commercial pharmacies were more likely to carry UPA than store-associated and independent pharmacies (11/84 [13%] vs. 1/61 [1%] vs. 0/20, respectively; P = 0.016). Most pharmacies that did not stock UPA reported that they could obtain it within 24 hours (94/153, 62%). Dedicated commercial pharmacies were most likely report the ability to obtain UPA in 24 hours (P = 0.016).ConclusionFew pharmacies stock UPA, the most effective form of oral emergency contraception. Enhanced communication between medical providers and pharmacists within current laws and regulations could enhance patient access to UPA.     

Colonization by S. Aureus increases the EASI and the number of appointments by patients with atopic dermatitis: cohort with 93 patients

BACKGROUND

Atopic dermatitis leads to epidermal barrier dysfunction and bacteria colonization. The relationship of the last factor with the severity of the disease and the frequency of exacerbation is not fully known.

OBJECTIVES

Verify the severity of the atopic dermatitis and the number of appointments generated by dermatosis, comparing patients colonized with patients not colonized by S. aureus. Verify the frequency of colonization by methicillin resistant Staphylococcus aureus acquired in the community.

METHODS

Cohort study with a 12 months follow-up, in a sample of patients from Porto Alegre, RS public network. Cultures in active injuries and nasal cavities were carried out as well as methicillin sensitivity tests to S. aureus. The severity of atopic dermatitis was defined by Eczema Area and Severity Index (EASI).

RESULTS

We included 93 patients, 43% female and 56% male, 26 colonized by S. aureus in the nasal orifices, 56 in the skin damage. The mean of initial Eczema Area and Severity Index was 5.5 and final 3.9. The initial Eczema Area and Severity Index of patients colonized by S. aureus in the skin and nasal cavity was larger than the number of patients without colonization(p< 0.05). During the period of one year, in average, there were six appointments/patient. There was linear correlation between the number of appointments during one year and the inicial Eczema Area and Severity Index (r = 0,78). There were no patients with methicillin resistant Staphylococcus aureus acquired in the community.

CONCLUSION

There is a relevant influence of staphylococcal colonization on the severity of atopic dermatitis and the number of appointments required by its exacerbation. Methicillin resistance among those affected by S. aureus does not seem to be an emergent problem, in this Brazilian sample.     

Neuroprotective effect of carnosine in the olfactory bulb after vanadium inhalation in a mouse model

Carnosine (β‐alanyl‐L‐histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attributed to oxidative damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, impairment of olfactory function has been described. Vanadium derivatives are environmental pollutants, and its toxicity has been associated with oxidative stress. Vanadium toxicity on the olfactory bulb was reported previously. This study investigates the neuroprotective effect of carnosine on the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided into four groups: vanadium pentoxide (V₂O₅) [0.02 mol/L] inhalation for one hour twice a week; V₂O₅ inhalation plus 1 mg/kg of carnosine administered daily; carnosine only, and the control group that inhaled saline. The olfactory function was evaluated using the odorant test. Animals were sacrificed four weeks after exposure. The olfactory bulbs were dissected and processed using the rapid Golgi method; cytological and ultrastructural analysis was performed and malondialdehyde (MDA) concentrations were measured. The results showed evidence of olfactory dysfunction caused by vanadium exposure and also an increase in MDA levels, loss of dendritic spines and necrotic neuronal death in the granule cells. But, in contrast, vanadium‐exposed mice treated with carnosine showed an increase in dendritic spines and a decrease in neuronal death and in MDA levels when compared with the group exposed to vanadium without carnosine. These results suggest that dendritic spine loss and ultrastructural alterations in the granule cells induced by vanadium are mediated by oxidative stress and that carnosine may modulate the neurotoxic vanadium action, improving the olfactory function.     

Search for Neuro-Endocrine Markers (Chromogranin A,Synaptophysin and VGF) in Breast Cancers. An integrated Approach Using Immunohistochemistry and Gene Expression Profiling

Discordant data are reported in the literature on the definition, incidence and clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour entity is currently assessed by immunohistochemistry (IHC) detecting “general” NE markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers have been considered as well. In the present study, in addition to CHGA and SYP, we investigated the expression of VGF, a neurotrophin-inducible gene, which is emerging as a new specific NE marker. In order to evaluate the differential expression of these neuro-endocrine markers in breast cancers, we conducted parallel immunohistochemical and gene expression analyses, using PCR, gene array and real-time quantitative PCR procedures. Data obtained in 28 cases were further validated with a meta-analysis of published datasets of 103 breast cancer cases. The value of IHC positivity (irrespective of the percentage of positive cells) was confirmed by over-expression of the related gene. However, the genetic approach emerged as more sensitive, showing over-expression of NE markers in a subset of IHC-negative carcinomas. In conclusion, the present study confirms, by a novel approach, the occurrence of NE differentiation in breast cancers. Over-expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a significant fraction (approximately 10 %) of infiltrative breast cancers.     

Coexistence of epidemic colistin-only-sensitive clones of Pseudomonas aeruginosa, including the blaSPM clone, spread in hospitals in a Brazilian Amazon City

Nosocomial outbreaks caused by multidrug-resistant (MDR) Pseudomonas aeruginosa have been associated to fibrocystic patients and isolates harboring metallo-beta-lactamase (MBL) genes. Genotyping is an important tool for interpreting bacterial nosocomial outbreaks and implementing adequate control strategies. The aim of this study was to evaluate whether an outbreak of MDR P. aeruginosa occurring in different hospitals was due to a unique clone or independent isolates. From 2000 to 2003, 108 P. aeruginosa were recovered from colonized/infected inpatients in hospitals of S?o Luís, Maranh?o, Brazil. The susceptibility test was performed with antipseudomonal drugs, and the presence of MBL genes were verified by PCR. Isolates were genotyped by pulsed-field gel electrophoresis (PFGE). The majority of strains was multiresistant including a great number presenting the colistin-only-sensitive (COS) profile. PFGE analysis revealed 54 genotypes, with predominance of three major COS clones (A, C, and E) coexisting at different moments and hospitals. Clone A harbored the bla(SPM) gene. Eight unique genotypes also had the COS profile. Other eight MDR genotypes presented isolates with differences in resistance profiles. Here we detected, for the first time, the coexistence of COS P.aeruginosa genotypes disseminated in several hospitals during long periods, attacking patients under various clinical conditions.