Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

Improving State-Mandated Breast Density Notifications

PurposeEffective written communication directly affects health care outcomes. Since 2016, the complex language of state-mandated breast density notifications (BDNs) has been challenged, because it is perceived to be beyond the comprehension of most patients. The aim of this study was to assess whether a revised BDN written at a lower reading grade level improves understanding compared with the current state-mandated BDN.MethodsA revised notification with similar content to the current state-mandated BDN was developed. Both notifications were presented to patients for direct comparison, using a paper survey asking questions that evaluated patients’ perceptions and convictions associated with breast density. Surveys were distributed at four outpatient imaging centers to screening mammography patients.ResultsThe current BDN’s mean readability metric was 13.4, and that of the revised BDN was 6.6. Five hundred surveys were analyzed. Survey data demonstrated that 56.6% of all women perceived that dense breast tissue results indicated a “high” associated lifetime breast cancer risk from the current state-mandated BDN compared with only 2.2% with the revised notification (P < .001). Nearly all women were more likely to initiate discussions with their providers regarding their breast tissue density after reading the revised notification (96.0%) as opposed to the current state-mandated BDN (32.8%; P < .001).ConclusionsA significant portion of women misinterpret the intended messages of the current state-mandated BDN. Thus, a revised notification at a lower reading grade level may improve understanding of breast density, leading to improved individualized breast cancer screening for women with dense breasts.     

Pseudocystic pilomatricoma: A new variant and review of the literature

A classic pilomatricoma, which usually presents with an asymptomatic, solitary, firm, subcutaneous nodule in the head, neck, or extremities of the paediatric population, is easily diagnosed based on its characteristic clinical and histopathological features. However, its variants often pose particular diagnostic challenges to clinicians due to their rarity and diverse clinicopathological features. We present a new pseudocystic variant, manifesting as solid lesions floating in a fluid‐filled sac.     

卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能和骨密度的影响分析

目的探究卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能、骨密度的影响。方法92例成人癫痫患者作为研究对象,随机分为左乙拉西坦组与卡马西平组,各46例。左乙拉西坦组采用左乙拉西坦治疗,卡马西平组采用卡马西平治疗。比较两组患者治疗前及治疗6个月后认知功能[语言智商(VIQ)、操作智商(PIQ)、总智商(FIQ)]评分、骨密度(腰椎、股骨大转子、股骨颈)变化情况。结果治疗6个月后,两组患者VIQ、PIQ、FIQ评分均较治疗前显著提升,且左乙拉西坦组患者VIQ评分(101.2±3.1)分、PIQ评分(108.1±2.3)分、FIQ评分(105.2±1.8)分均明显高于卡马西平组的(95.1±2.8)、(94.1±2.0)、(93.5±1.6)分,差异有统计学意义(P<0.05)。治疗6个月后,卡马西平组患者腰椎、股骨大转子、股骨颈骨密度均较治疗前显著下降,且明显低于卡马西平组,差异有统计学意义(P<0.05);左乙拉西坦组治疗6个月后腰椎、股骨大转子、股骨颈骨密度与治疗前比较差异无统计学意义(P>0.05)。结论左乙拉西坦与卡马西平治疗成人癫痫,左乙拉西坦更能明显提升患者认知功能,且对患者骨密度无影响。     

Role of optical coherence tomography angiography in the characterization of vascular network patterns of ocular surface squamous neoplasia

PurposeTo visualize and quantify vascular networks in individuals with ocular surface squamous neoplasia (OSSN) through optical coherence tomography angiography (OCTA).MethodCross-sectional study of OSSN patients. Vascular networks were measured by OCTA in the epithelium and sub-epithelial space in the tumors, adjacent tissue, and in the contralateral eye. Vessel area density (VAD, percent of blood vessels within 2.14 mm²), was calculated for each location. Total tumor density (TTD, percent of blood vessels within the entire tumor) was calculated. VAD was assessed separately for corneal and conjunctival locations and compared.ResultsFifteen patients with OSSN were included. The mean age was 61 ± 12 years and the majority were male (80%). The mean tumor area, volume, depth, and TTD were 28.0 ± 9.0 mm² (range, 10.9–39.7), 9.1 ± 4.1 mm³ (range, 3.4–18.8), 334 ± 125 μm (range, 177–571), and 33.2% ± 11.0% (range, 18.7–58.8), respectively. The VAD was highest within the tumor (28.9% ± 8.7%) followed by the adjacent sub-epithelial tissue and the tissue underneath the conjunctival component of tumor. These densities were higher than the VAD in the tissues of the non-involved eye (all P < 0.05). The VAD within conjunctival component of tumor was significantly higher than those with corneal component (29.8% ± 9.5% vs. 21.1% ± 5.5%, p = 0.006). The VAD under conjunctival tumor was also significantly higher than under corneal component (24.1% ± 7.8% vs. 17.0% ± 6.1%, p = 0.024).ConclusionsOCTA imaging allowed for visualization and quantification of vessel structure and density within, under, and surrounding OSSN.     

OCTA对青少年近视人群视网膜微血管密度的观察

目的：基于光学相干断层扫描血管成像（OCTA）技术探讨青少年儿童近视与视网膜表层微血管密度 及视网膜厚度的相关性。方法：横断面研究。共纳入2018年5─11月于四川大学华西医院眼科门 诊就诊的7～14岁青少年近视患者105例（193眼）。对所有受检者进行光学相干断层扫描（OCT）和 OCTA检查，量化分析黄斑中心凹视网膜厚度和各部位视网膜表层微血管密度。单因素方差分析比 较低、中、高度近视组各部位视网膜微血管密度及视网膜厚度的差异。采用Pearson相关系数探讨视 网膜厚度与各部位视网膜表层微血管密度的相关性。Spearman相关系数用于探讨等效球镜与中心凹、 旁中心凹视网膜表层微血管密度以及视网膜厚度的关系；分段多项式函数分析等效球镜度与外环及 直径6 mm完整视网膜表层微血管密度的关系。结果：旁中心凹、外环、直径6 mm完整区域视网膜 表层微血管密度在低、中、高度近视组间比较差异均具有统计学意义（F=11.651、14.499、14.232， 均P<0.001）。年龄与中心凹视网膜厚度之间有较弱正相关关系（r=0.187，P=0.011），与各部位微血管 密度均无相关性。等效球镜度与旁中心凹视网膜微血管密度有相关性（r=-0.301，P<0.001），与外环、 直径6 mm完整区域视网膜表层微血管密度呈曲线相关（r=-0.319，P<0.001；r=-0.307，P<0.001）。 但与中心凹视网膜表层微血管密度及视网膜厚度无显著相关性。此外，中心凹处视网膜厚度与微血 管密度呈正相关（r=0.691，P<0.001），与其余部位微血管密度无相关性。结论：青少年近视程度数 与旁中心凹、外环及直径6 mm完整区域视网膜表层微血管密度呈负相关；中心凹处视网膜厚度与年 龄、微血管密度呈正相关。