基于肿瘤浸润深度及大小的TTS 评分系统对可切除胃癌患者预后判断的价值

目的:探讨基于肿瘤浸润深度及大小的TTS评分系统对可切除胃癌患者预后判断的价值。方法:选择行根治性切除的234例胃癌患者为研究对象。根据肿瘤浸润深度（T分期）和肿瘤大小构建TTS评分系统，分为TTS 0级、1级、2级，代表肿瘤侵袭性逐渐升高。通过Cox多因素模型分析TTS评分系统作为预后判断工具的可行性。结果:T1-T4期患者肿瘤的平均大小分别为(3.3±2.7)cm、(4.1±3.1)cm、(6.6±3.1)cm、(9.4±4.9)cm。单因素分析显示，肿瘤浸润深度与肿瘤大小、淋巴结转移、TNM分期、淋巴浸润和血管浸润显著相关(P＜0.01)。ROC曲线显示，45 mm为肿瘤大小的最佳界值，可有效区分患者是否存在淋巴结转移，曲线下面积(area under curve,AUC)为0.762。综合肿瘤大小的临界值和肿瘤浸润深度，构建TTS评分系统,TTS 0级、TTS 1级和TTS 2级的患者5年生存率分别为95.6%、83.3%和70.2%，两两比较后发现，不同TTS状态患者的生存率之间均存在显著差异(P＜0.01)。Cox多因素分析发现，TTS评分是影响患者预后的独立性危险因素（P＜0.05）。结论:本研究根据肿瘤浸润深度和大小构建了TTS评分系统，并证明了TTS评分与胃癌患者的预后密切相关。     

Articular degeneration after subchondral cementation for giant cell tumors at the knee

PurposeTo quantify joint degeneration and the clinical outcome after curettage and cementation in subchondral giant cell tumors of the bone (GCTB) at the knee.MethodsWe conducted a retrospective analysis of 14 consecutive patients (seven female, seven male) with a mean age of 34 years (range 19–51) who underwent curettage and subchondral cementation for a biopsy-confirmed GCTB at the distal femur or the proximal tibia between August 2001 and August 2017, with a mean follow-up period of 54.6 months (range 16.1–156 months). The Whole-Organ Magnetic Resonance Imaging Score (WORMS), Kellgren-Lawrence (KL) classification, and Musculo-Skeletal Tumor Society (MSTS) score were assessed.ResultsRadiological degeneration progressed from preoperative to the latest follow-up, with a median WORMS from 2.0 to 4.0 (p = 0.006); meanwhile, the median KL score remained at 0 (p = 0.102). Progressive degeneration (WORMS) tended to be associated with the proximity of the tumor to the articular cartilage (mean 1.57 mm; range 0–12 mm) (p = 0.085). The most common degenerative findings were cartilage lesions (n = 11), synovitis (n = 5), and osteophytes (n = 4). Mean MSTS score increased from 23.1 (preoperatively) to 28.3 at the latest follow-up (p < 0.01).Seven patients (50%) were treated for a local recurrence, with six revision surgeries performed. Removal of the cement spacer and filling of the cavity with a cancellous autograft was performed in seven patients. Conversion to a total knee arthroplasty was performed in one patient for local tumor control.ConclusionsCementation following the curettage of GCTB around the knee is associated with slight degeneration at medium-term follow-up and leads to a significant reduction in pain. Removal of the cement and reconstruction with an autograft may be beneficial in the long term.     

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database

IntroductionThe potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population.MethodsFrom the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS).ResultsOf 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group.ConclusionsThe use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.     

GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity

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Dendritic cells can prime anti-tumor CD8+ T cell responses through major histocompatibility complex cross-dressing

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Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

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Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.