常见妇科疾病引起的雌激素水平变化与骨转换的关系

女性常见的妇科疾病如子宫内膜异位症、子宫内膜癌、乳腺癌、Sheehan综合征等,其病程中体内雌激素水平变化,直接或间接地影响骨转换水平,导致骨量变化。本文研究不同疾病状态下,疾病本身因素或手术及药物治疗对女性卵巢功能和雌激素水平的影响,从而影响骨转换率,导致继发性骨质疏松。有助于预防和治疗女性激素相关性骨量下降和骨质疏松,提高女性患者的生活质量。     

Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved on PET/CT

OBJECTIVE: A potential source of false-positive FDG PET interpretations in oncologic imaging is FDG uptake in brown fat. The purpose of this study was to determine the prevalence, location, and appearance of hypermetabolic brown fat in the mediastinum. MATERIALS AND METHODS: All PET/CT scans obtained at our cancer institution from August to October 2003 were retrospectively reviewed for increased FDG uptake in the mediastinum localized to fat on CT. The following features were recorded: location, appearance, maximal standard uptake value (SUV(max)) of hypermetabolic mediastinal brown fat, and presence of extramediastinal brown fat. RESULTS: PET/CT scans were obtained in 845 oncologic patients. Fifteen patients (1.8%) with focal hypermetabolic mediastinal brown fat were identified: nine women and two men (age range, 27-79; mean, 55.1 years) and four children (age range, 5-16 years; mean, 10 years). Hypermetabolic mediastinal brown fat (mean SUV(max), 5.7) was more common in children (4/8) than in adults (11/837) and more common in women (9/372) than in men (2/465). Foci of hypermetabolic brown fat were localized to the paratracheal, paraesophageal, prevascular, and pericardial regions; interatrial septum; and azygoesophageal recess. Five patients had focal hypermetabolic brown fat isolated to the mediastinum. Ten patients also had extramediastinal hypermetabolic brown fat in the neck, thorax, and abdomen. There was no difference in the body weight (p = 0.876) or body mass index (p = 0.538) of patients with hypermetabolic brown fat compared with age- and sex-matched control subjects. CONCLUSION: Hypermetabolic brown fat can be localized to the mediastinum and manifests as focal increased FDG uptake. Knowledge of this potential pitfall and precise localization with fusion PET/CT are important in preventing misinterpretation as malignancy.     

Expanding Awareness of the Distribution and Biologic Potential of Ectomesenchymal Chondromyxoid Tumor

Ectomesenchymal chondromyxoid tumor is a rare neoplasm of uncertain histogenesis that typically occurs in the anterior dorsal tongue. Recent reports in the literature have described rare examples of gingival, palatal and tonsillar lesions. Histologically, ectomesenchymal chondromyxoid tumors are typically well-circumscribed, lacking overtly aggressive features. Herein we report a tumor arising in the right mandible that is morphologically and molecularly consistent with ectomesenchymal chondromyxoid tumor. This case furthers awareness of the extra-glossal distribution of this neoplasm; moreover, it suggests that a subset of these tumors have the potential for locally aggressive behaviour.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01169-5) contains supplementary material, which is available to authorized users.     

Adenosine A(2A) receptor activation prevents progressive kidney fibrosis in a model of immune-associated chronic inflammation

Crescentic glomerulonephritis (GN) in Wistar-Kyoto rats progresses to lethal kidney failure by macrophage (Mφ)-mediated mechanisms. Mφs in nephritic glomeruli express adenosine A(2A) receptors (A(2A)Rs), the activation of which suppresses inflammation. Here, we pharmacologically activated the A(2A)Rs with a selective agonist, CGS 21680, and inactivated them with a selective antagonist, ZM241385, to test the effects on established GN. When activation was delayed until antiglomerular basement membrane GN and extracellular matrix deposition were established, glomerular Mφ infiltration was reduced by 83%. There was also a marked improvement in glomerular lesion histology, as well as decreased proteinuria. A(2A)R activation significantly reduced type I, III, and IV collagen deposition, and E-cadherin expression was restored in association with a reduction of α-smooth muscle actin-positive myofibroblasts in the interstitium and glomeruli. In contrast, pharmacological inactivation of A(2A)Rs increased glomerular crescent formation, type I, III, and IV collagen expression, and enhanced E-cadherin loss. Activation of A(2A)Rs suppressed the expression of the Mφ-linked glomerular damage mediators, transforming growth factor-β, osteopontin-1, thrombospondin-1, and tissue inhibitor of metalloproteinase-1. Thus, A(2A)R activation can arrest GN and prevent progressive fibrosis in established pathological lesions.     

Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative,HER2-Positive Breast Cancer

Background

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.

Methods

Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.

Results

Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.

Conclusions

BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups.     

De novo minimal change disease associated with reversible post-transplant nephrotic syndrome. A report of five cases and review of literature

Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be related to a large variety of glomerular lesions. In some of these cases, the transplant biopsy showed no significant glomerular changes and the NS was reversible, but the primary renal disease was not minimal change disease (MCD), suggesting that MCD may develop de novo in renal transplant setting. Knowledge of this entity, however, is limited. Among 67 cases of post-transplant NS encountered in a 12-yr period, five were found to be associated with de novo MCD. A critical review of the literature revealed nine additional cases of de novo MCD. The data from these 14 cases show that patients with de novo MCD had a large variety of primary renal diseases but MCD or focal segmental glomerulosclerosis was not among them. Eight of the 14 transplanted kidneys (60%) were from living related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3-76 g/d) developed immediately or shortly after transplantation (within 4 months for all reported cases, except for one at 24 months). The serum creatinine when NS was first diagnosed was normal or mildly elevated, but acute renal failure occurred in three patients. On biopsy, the glomeruli were normal or, more frequently, displayed mild, focal segmental mesangial sclerosis, hypercellularity, deposition of IgM/C3, or accumulation of mononuclear inflammatory cells in some glomerular capillaries. The tubulointerstitial compartment was normal in cases with normal renal function; displayed mild acute and/or chronic rejection that correlated with a mildly elevated serum creatinine; or showed acute changes including acute rejection, acute tubular necrosis, or acute cyclosporin A toxicity, which accounted for both acute renal failure at presentation and its subsequent reversibility. Under various treatments, including increased steroids, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers, sustained remission of NS was achieved in 13 cases, within a year (0.5-12 months) in 10 and later (24, 34 and 98 months, respectively) in three. In the remaining case, the patient died of septic shock 2 months after transplantation. After remission of the NS, the grafts functioned well without or with minimal proteinuria for several years. De novo MCD has characteristic clinical and pathologic features. It represents an important but hitherto underemphasized cause of post-transplant NS, which is potentially reversible and does not adversely affect the renal transplants.     

Activation of adenosine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: therapeutic implications for Parkinson's disease

It is anticipated that further understanding of the protective mechanism induced by ischemic preconditioning will improve prognosis for patients of ischemic injury. It is not known whether preconditioning exerts beneficial actions in neurodegenerative diseases, in which ischemic injury plays a causative role. Here we show that transient activation of ATP-sensitive potassium channels, a trigger in ischemic preconditioning signaling, confers protection in PC12 cells and SH-SY5Y cells against neurotoxic effect of rotenone and MPTP, mitochondrial complex I inhibitors that have been implicated in the pathogenesis of Parkinson's disease. The degree of protection is in proportion to the bouts of exposure to an ATP-sensitive potassium channel opener, a feature reminiscent of ischemic tolerance in vivo. Protection is sensitive to a protein synthesis inhibitor, indicating the involvement of de novo protein synthesis in the protective processes. Pretreatment of PC12 cells with preconditioning stimuli FeSO(4) or xanthine/xanthine oxidase also confers protection against rotenone-induced cell death. Our results demonstrate for the first time the protective role of ATP-sensitive potassium channels in a dopaminergic neuronal cell line against rotenone-induced neurotoxicity and conceptually support the view that ischemic preconditioning-derived therapeutic strategies may have potential and feasibility in therapy for Parkinson's disease.     

The origin of DNA replication and Fieller's problem

The paper considers the statistical problem of estimating the origin of DNA replication within the human ribosomal DNA (rDNA) locus and the issue of assessing the standard error of the estimate. Based on mapping the cumulative replication index (CRI), two different modelling schemes are suggested and investigated. The statistical problem of constructing a confidence interval for the origin of DNA replication is related to Fieller's problem of obtaining a confidence interval for the ratio of two normal means. Standard normal theory, the delta and bootstrap methods are used to estimate the standard error of the estimate of the origin of DNA replication, as well as the variation of the replication rate.     

Improving the consistency in cervical esophageal target volume definition by special training

PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. RESULTS: There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. CONCLUSION: For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.