Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003–2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P < 0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P = 0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P = 0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.     

Exclusion of Patients With Brain Metastases in Published Phase III Clinical Trials for Advanced Breast Cancer

Metastatic HER2-positive (HER2+) and triple-negative breast cancer (TNBC) confer a 30% or higher risk of developing brain metastases (BrM), but BrM is typically an exclusion criteria for clinical trials, which limits the generalizability of trial results to these patients. We therefore analysed trends in the enrollment of patients with BrM, as well as the use of outcomes specific to the central nervous system (CNS), in phase III clinical trials evaluating systemic therapy for patients with advanced HER2+ and/or TNBC. Notably, 10 of the 34 trials (29%, 95% confidence interval = 15.1%-47.5%) evaluated CNS-specific outcomes and trials that completely excluded patients with BrM were significantly less likely to meet their primary endpoint (n = 6/17, 35%) than those that permitted conditional enrollment (n = 13/15, 87%) (P = .005), suggesting that enrollment of patients with BrM is not detrimental to trial success.     

接受机械取栓治疗的急性脑梗死患者血栓特征研究进展

急性脑梗死是威胁我国人民健康的重大疾病,其致死率及致残率均较高,造成了沉重的社会负担。及时开通导致梗死的责任血管以恢复脑灌注是治疗该病的关键。机械取栓技术的应用使得患者的血栓组织能够被获取并得到研究。本文介绍了近年来通过机械取栓术获取的血栓的相关研究发现,以纤维蛋白为主的血栓是造成取栓困难的重要组织学原因,影像学方法可以在术前评估血栓特征。这些发现提示临床工作者可以积极开发新型血栓取出装置用于处理难治性血栓,并有必要探索精确便捷的血栓特征影像学评价方法,从而提高机械取栓疗效。     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

基于生物信息学筛选早发性乳腺癌差异表达基因

目的筛选并分析与早发性乳腺癌发生、发展相关的靶基因。 方法(1)在美国国立生物技术信息中心的公共基因芯片数据库(GEO)中检索早发性乳腺癌样本及非早发性乳腺癌样本相关基因芯片数据。对上述数据使用GEO2R、R4.1.2及Venn软件筛选出相关差异表达基因(DEGs)，并运用在线分析工具(Web Gestalt)对DEGs，进行相关功能和信号通路富集分析。(2)同时，通过String在线数据库构建DEGs编码的蛋白质-蛋白质相互作用(PPI)网络，并利用Cytohubba插件对该网络中的基因进行评分，筛选出枢纽基因。将枢纽基因导入Kaplan-Meier生存分析工具(Kaplan-Meier Plotter)，评估枢纽基因在早发性乳腺癌的预后价值。(3)将肿瘤基因组图谱(TCGA)数据库中的肿瘤组织以年龄为标准进行分组，分析枢纽基因在各年龄组中的表达，并与正常组织中的表达进行比较，对得到的枢纽基因进行验证。DEGs表达量的多组间比较使用Kruskal-Wallis H检验，使用Bonferroni法进行两两比较。 结果(1)筛选出编号为GSE89116、GSE109169、GSE36295的基因芯片数据集，共得到80个差异表达基因，其中上调差异表达基因17个，下调差异表达基因63个。富集分析显示：DEGs主要富集在脂质代谢和氧化还原过程以及PPAR信号通路、AMPK信号通路上。(2)在PPI中发现主要的关键基因为PPARG、ADIPOQ、LIPE、PCK1、PDK4、ACACB、PLIN1、CAV1、CD36、ANGPTL4。ACACB、ADIPOQ、CAV1、LIPE、PLIN1、PPARG基因的低表达与乳腺癌患者的不良OS相关(HR＝0.69、0.84、0.76、0.88、0.78、0.82；95%CI：0.59~0.80、0.76~0.93、0.67~0.83、0.79~0.97、0.70~0.86、0.73~0.90；P均<0.050)。(3)ACACB、ADIPOQ、LIPE、PLIN1、CAV1及PPARG这6个与预后相关的基因在正常组织中的表达量均远高于各年龄组肿瘤组织中的表达量(χ²＝104.03、179.57、161.85、189.87、118.56、103.62，P均<0.001)，早发性乳腺癌组(21~40岁)的LIPE、PLIN1表达量低于41~60岁、61~80岁年龄组，差异具有统计学意义(LIPE: Z＝21.07、23.12, P均<0.050; PLIN1：Z＝16.89、18.76, P均<0.050)。 结论早发性乳腺癌与非早发性乳腺癌存在差异基因表达谱，LIPE、PLIN1可能是早发性乳腺癌发生、发展的关键基因。     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Constructing queer mother‐knowledge and negotiating medical authority in online lesbian pregnancy journals

Medical interactions around reproduction are increasingly extending beyond the physician's office and onto the Internet, where negotiation with medical authority occurs in complex and dynamic ways. Recently, scholars have noted the Internet's potential for creating spaces where women can dialogue with and reconstruct medical authority, yet this growing body of work is overwhelming heteronormative. This paper thus interrogates how lesbian women use the Internet to challenge, deploy, and rework medical authority around reproduction while navigating the transition to parenthood. I draw from 17 online journals authored by lesbian couples during the conception, pregnancy, and birth of their first child, each spanning between 18 months and 2 years, in order to understand how the transition process unfolds over time. I argue that lesbian couples engage with medical authority when seeking affirmation and normalisation yet discard and publicly reject the heteronormative assumptions that accompany reproductive medicine. Further, they chart a new process that I term ‘constructing queer mother‐knowledge’, in which they critique and balance knowledges from institutionalised medicine, their own bodies, and their queer communities. With this new concept, I complicate understandings of lesbian mothers‐to‐be and their interactions with medical authority as they build subversive families.