Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

PURPOSE: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts. METHODS: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay. RESULTS: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF. CONCLUSIONS: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.

High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia.

AIM: This study examined the prevalence of neurological impairment and pituitary hormone deficiency (PHD) in patients with unilateral and bilateral optic nerve hypoplasia (ONH). METHODS: A population-based cross-sectional cohort study of 65 patients (51% female) with ONH was conducted in Stockholm. Of these were 35 bilateral and 30 unilateral. The patients were below 20 years of age, living in Stockholm in December 2009 and found through database searching. The median age at the analysis of the results in January 2018 was 16.1 years (range 8.1-27.5 years). Neurological assessments and blood sampling were conducted, neuroradiology was reviewed and growth curves were analysed. Diagnoses of PHDs were based on clinical and biochemical evidence of hormone deficiency. RESULTS: Neurological impairments were identified in 47% of the patients and impairments in gross and fine motor function were more prevalent in bilateral ONH (p < 0.001). In addition, 9% had cerebral palsy and 14% had epilepsy. The prevalence of PHD was 29 and 19% had multiple PHD. CONCLUSION: Children with ONH had a high risk of neurological impairment, especially in bilateral disease. Both unilateral and bilateral ONH signified an increased prevalence of PHD and all these children should be endocrinologically followed up until completed puberty.

Decline in executive functions and speed in suspected low-grade gliomas: A 3-year follow-up of a clinical cohort.

Changes over time in information processing speed and executive functions (EFs) were studied in patients with suspected low-grade gliomas (LGG) 3 years after diagnosis. Using a person-oriented approach, the study aimed at focusing solely on two cognitive domains known to be significant in the understanding of the impact of white matter diseases. The Barkley's hybrid model of EFs was used as a theoretical framework for the evaluation of EFs. The majority of the patients showed a decline in at least one of these two cognitive domains indicating that the progress of diffuse brain injury cannot be neglected in understanding neuropsychological changes over time in patients with LGG. In our sample, higher age and radiological signs of radiotherapy-induced brain atrophy were seen in patients with a decline in both domains.

Reliability in the assessment of tendon volume and intratendinous signal of the Achilles tendon on MRI: a methodological description.

The purpose is to introduce a method for accurately and objectively evaluating volume and mean intratendinous signal within the Achilles tendon using MRI. We prospectively studied MRI from 33 patients with chronic Achilles tendinosis (20 males and 13 females) with a median age of 52 years (range 29-70). In all patients, both Achilles tendons were investigated with T1-WI as well as PD-WI MRI. Thus, 66 Achilles tendons were evaluated in the study. Tendon volume and mean intratendinous signal were evaluated using a computerized 3-D seed-growing technique. In general, the computerized 3-D seed-growing technique resulted in an excellent overall observer reliability of the MRI-measurements. The reliability (R) for tendon volume measurements was highest for the T1-WI sequence (R=97.9%). For the mean intratendinous signal, the PD-WI sequence showed the highest reliability (R=88.1%). The same pattern was present when we studied the coefficient of variation (CV). For the CV, lower figures indicate more reliable estimates. CV was 4.9% for tendon volume and 8.9% for mean intratendinous signal. In conclusion, it could be said that a computerized 3-D seed-growing technique to monitor and evaluate the volume of the Achilles tendon and mean intratendinous signal, using MRI, shows an overall excellent reliability regarding inter- as well as intra-observer reliability.

Invasive breast cancer: correlation of dynamic MR features with prognostic factors.

The purpose of this exploratory study was to correlate kinetic and morphologic MR features with histologic prognostic factors in invasive breast cancer. Sixty-one women with invasive breast cancer underwent dynamic contrast-enhanced MR imaging at 1.5 T, using T1-weighted 3D fast low-angle shot technique. The MR characteristics were correlated with classical pathologic prognostic factors (tumor size, histologic type, grade and lymph node status) and immunohistochemically detected biomarkers [c-erbB-2, p53, Ki-67, and estrogen receptor (ER)]. Univariate and multivariate statistical analyses were performed. Presence of rim enhancement pattern, early maximal enhancement and washout phenomenon were independently associated with established predictors of poor prognosis (higher histologic grade, positive Ki-67, and negative ER status). Our results suggest that these MR signs are not only important in differentiating benign from malignant lesions, but may also be useful to noninvasively identify highly aggressive breast carcinomas.