Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator.

BACKGROUND: Intravaginal estradiols (VE) have been proposed as safe alternatives to systemic estrogen therapy in breast cancer survivors. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor-positive breast cancer or at high risk for breast cancer (n = 24) who were taking an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) and VE for ≥ 90 days for atrophic vaginitis and 24 controls taking AI only participated in the study. Serum samples were drawn from VE ring patients before insertion and 30 and 60 days postinsertion, from VE tablet patients the morning before insertion and approximately 12 hours postinsertion, and once from controls. Samples were assayed for E2 concentrations by using highly sensitive radioimmunoassay after ether extraction. RESULTS: Mean E2 levels in controls were 3.72 pmol/L (range, < 3.0-7.7 pmol/L); mean E2 levels preinsertion and 12 weeks postinsertion in the VE ring patients were significantly greater than controls (P < .001 for each comparison). Mean preinsertion E2 levels in patients using VE tablets were not significantly different than those of controls (P = .48), and postinsertion levels were 76 pmol/L higher than preinsertion (P < .001). CONCLUSION: VE treatment increased E2 levels. Preinsertion levels for patients receiving VE tablets were not elevated compared with those of controls, suggesting that E2 elevations with this preparation may not be continuously sustained. We conclude that VE treatment, regardless of type, results in elevated circulating E2 levels in this population and should be used with caution.

Developing a nanoparticle test for prostate cancer scoring.

BACKGROUND: Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate tumor aggressiveness are rather limited. METHOD: We report here for the first time the development of a nanoparticle test that not only can distinguish prostate cancer from normal and benign conditions, but also has the potential to predict the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a blood serum or human IgG solution and the spiked sample is incubated with a citrate-protected gold nanoparticle solution. IgG is known to adsorb to citrate-protected gold nanoparticles to form a "protein corona" on the nanoparticle surface. From this study, we discovered that certain tumor-specific molecules can interact with IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution and detected by a dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for multiple variant analysis, and using the Student t-test or nonparametric Mann-Whitney U-tests for pairwise analyses. RESULTS: An inverse, quantitative correlation of the average nanoparticle size of the assay solution with tumor status and histological diagnostic grading was observed from the nanoparticle test. IgG solutions spiked with prostate tumor tissue exhibit significantly smaller nanoparticle size than the solutions spiked with normal and benign tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The test particularly revealed large differences among the intermediate Grade 2 tumors, and suggested the need to treat them differently. CONCLUSION: Development of a new nanoparticle test may provide a quantitative measure of the prostate cancer aggressiveness. If validated in a larger study of patients with prostate cancer, this test could become a new diagnostic tool in conjunction with Gleason Score pathology diagnostics to better distinguish aggressive cancer from indolent tumor.

Toward an integrated knowledge environment to support modern oncology.

Around the world, teams of researchers continue to develop a wide range of systems to capture, store, and analyze data including treatment, patient outcomes, tumor registries, next-generation sequencing, single-nucleotide polymorphism, copy number, gene expression, drug chemistry, drug safety, and toxicity. Scientists mine, curate, and manually annotate growing mountains of data to produce high-quality databases, while clinical information is aggregated in distant systems. Databases are currently scattered, and relationships between variables coded in disparate datasets are frequently invisible. The challenge is to evolve oncology informatics from a "systems" orientation of standalone platforms and silos into an "integrated knowledge environments" that will connect "knowable" research data with patient clinical information. The aim of this article is to review progress toward an integrated knowledge environment to support modern oncology with a focus on supporting scientific discovery and improving cancer care.

Acute intraprocedural thrombus formation during wingspan intracranial stent placement for intracranial atherosclerotic disease.

BACKGROUND: Treatment of intracranial atherosclerotic disease with the Wingspan-Gateway intracranial stent and balloon angioplasty system has been reported in several multicenter registries. To date, the incidence of acute intraprocedural thrombus formation during Wingspan stent placement has not been reported. OBJECTIVE: We reviewed the incidence of acute thrombus formation, treatment, and outcome for patients who underwent Wingspan stent placement by the senior author (B.L.H.) between June 2006 and April 2009. METHODS: We routinely perform angiograms every 10 minutes for at least 30 minutes after placement of a Wingspan stent to check for acute thrombus formation. Acute thrombus was graded: (1) visible thrombus but not flow limiting, (2) visible and flow-limiting thrombosis, and (3) complete stent occlusion. Recanalization was graded according to Thrombosis In Myocardial Infarction score. RESULTS: Forty-one patients underwent Wingspan stent placement for intracranial stenosis. Acute intraprocedural thrombus formation developed in 6 (14.6%) within 20 minutes after stent placement: 3 grade 1, 1 grade 2, and 2 grade 3. All 6 were successfully recanalized with Thrombosis In Myocardial Infarction score 3 after intravenous abciximab with or without intra-arterial tissue plasminogen activator and/or balloon angioplasty. There was no morbidity, and all 6 patients were discharged home at their neurological baseline. CONCLUSION: We recommend serial angiography every 10 minutes for at least 30 minutes after placement of Wingspan stents. Once detected, acute thrombosis can be successfully treated with intravenous abciximab with or without intra-arterial tissue plasminogen activator and/or balloon angioplasty.

Radiographic and pathologic findings in an atypical brainstem variant of reversible posterior leukoencephalopathy syndrome.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) and hypertensive encephalopathy (HE) are terms generally used interchangeably to describe a syndrome characterized by encephalopathy, focal deficits, and vasogenic edema seen on magnetic resonance imaging, which are potentially reversible with treatment. The underlying pathologic changes are less well defined. Previously, the only pathologic data available came from a single autopsy series. Results from a recent biopsy report differ with the autopsy series leading to the suggestion that RPLS and HE may be distinct. CASE REPORT: We report a markedly hypertensive patient with encephalopathy and hemiparesis and focal edema in the brainstem visualized on magnetic resonance imaging. A biopsy was performed that demonstrated pathologic changes associated with RPLS. With treatment of hypertension, the patient's symptoms resolved completely. CONCLUSIONS: We report an unusual brainstem variant of RPLS, adding to the neuropathologic features of this syndrome, and supporting the predominant view that RPLS and HE have a shared pathologic basis.

Steroid treatment of primary progressive aphasia.

OBJECTIVE: To learn if oral steroid treatment can alter the signs of primary progressive aphasia (PPA). Many patients with PPA have had a vasectomy and there is a possible link between vasectomy and autoimmune diseases. If PPA is, at least in part, an autoimmune disease, patients might improve with immunosuppressant treatment. DESIGN: Case report. SETTING: Cognitive and memory clinic. PATIENT: A 68-year-old right-handed man with a 2.5-year history of progressive speech impairment who had a vasectomy 25 years prior. RESULTS: Examination revealed that he had a nonfluent aphasia with intact repetition and comprehension. Before and during oral prednisone treatment, he was assessed for speech fluency, naming, and episodic and working memory. All assessments except episodic memory showed a dramatic improvement. On reassessment 1 month after discontinuing treatment, the patient's performance on cognitive testing had regressed toward baseline. CONCLUSIONS: Although this patient's improvement with steroid treatment provides support for the postulate that PPA might be a treatable autoimmune disease, future placebo-controlled trials are needed before conclusions can be drawn.

Study of sexual functioning determinants in breast cancer survivors.

Our goal was to identify the treatment, personal, interpersonal, and hormonal (testosterone) factors in breast cancer survivors (BCSs) that determine sexual dysfunction. The treatment variables studied were type of surgery, chemotherapy, radiation, and tamoxifen. The personal, interpersonal, and physiologic factors were depression, body image, age, relationship distress, and testosterone levels. A sample of 55 female breast cancer survivors seen for routine follow-up appointments from July 2002 to September 2002 were recruited to complete the Female Sexual Functioning Index (FSFI), Hamilton Depression Inventory (HDI), Body Image Survey (BIS), Marital Satisfaction Inventory-Revised (MSI-R), a demographic questionnaire, and have a serum testosterone level drawn. The average time since diagnosis was 4.4 years (SD 3.4 years). No associations were found between the type of cancer treatment, hormonal levels, and sexual functioning. BCS sexual functioning was significantly poorer than published normal controls in all areas but desire. The BCSs' level of relationship distress was the most significant variable affecting arousal, orgasm, lubrication, satisfaction, and sexual pain. Depression and having traditional role preferences were the most important determinants of lower sexual desire. BCSs on antidepressants had higher levels of arousal and orgasm dysfunction. Women who were older had significantly more concerns about vaginal lubrication and pain. Relationship concerns, depression, and age are important influences in the development of BCS sexual dysfunction. The relationship of testosterone and sexual dysfunction needs further study with larger samples and more accurate assay techniques.

Estrogen replacement therapy in breast cancer survivors: a matched-controlled series.

OBJECTIVE: We prospectively administered estrogen replacement therapy (ERT) to control estrogen deficiency symptoms in breast cancer survivors as part of our clinical practice. We report the consequences of ERT compared with a historical matched-control group. DESIGN: Two hundred seventy-seven disease-free survivors received ERT. Controls were matched for exact stage, a recurrence-free period similar to the period to ERT initiation in the ERT group, approximate age, and duration of follow-up. The mean time from breast cancer diagnosis to initiation of ERT was 3.61 (+/- 0.25) years, with a median of 1.88 years. The mean duration of ERT was 3.7 (+/- 3.01) years, with a median of 3.05 years. RESULTS: Hot flashes were relieved in 206 of 223 women (92%), dyspareunia/vaginal dryness in 149 of 167 women (89%), and reactive depression/anxiety/mood change in 111 of 126 women (88%). Univariate analysis demonstrated no statistical differences between the groups for age, stage, pathology at diagnosis, progesterone receptor status, local therapy, breast at risk, prior chemotherapy, and duration of follow-up. The ERT group was more likely to be estrogen receptor negative (P = 0.01), to have received prior ERT (P < 0.001), and to have received no adjuvant tamoxifen (P < 0.001). There was no significant difference between the ERT and control groups in ipsilateral primary/recurrence (5/155 v 5/143; P = 0.85), contralateral breast cancers (10/258 v 9/260; P = 0.99), or systemic metastasis (8/277 v 15/277; P = 0.13). Noncause-specific deaths in the control group numbered 15 (of 277), and in the ERT group, 7 (of 277) (P = 0.03). Overall survival favored the ERT group (P = 0.02). CONCLUSIONS: In these selected patients, ERT relieved estrogen deficiency symptoms and did not increase the rate or time to an ipsilateral recurrence/new primary, contralateral new primary, local-regional recurrence, or systemic metastases.