Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors.MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed.Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n = 9), bladder tumor (n = 7), testis tumors (n = 4), and prostate cancer (n = 2). There was no intraoperative complication. Postoperative complications were seen in 2 patients.ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.     

超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)治疗血友病性关节病

目的 观察超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（益赛普）治疗血友病性关节病（HA）的价值。方法 回顾性分析32例接受超声引导下穿刺关节腔注射益赛普的HA患者，对比观察治疗前及治疗后1个月血友病关节健康评分（HJHS）、视觉模拟评分（VAS），以及超声所示目标关节增生滑膜厚度、血流信号、Melchiorre及中国早期血友病性关节病超声检测（HEAD-US-C）评分，评估其治疗价值。结果 对32例均成功完成超声引导下穿刺关节腔及腔内注射益赛普，共对18例膝关节、7例肘关节及7例踝关节进行治疗。术后未出现感染、出血等并发症。治疗后1个月，目标关节HJHS、VAS、Melchiorre评分、HEAD-US-C评分及增生滑膜最大厚度、平均厚度、血流信号均低于治疗前（P均<0.01）。结论 超声引导下关节腔内注射益赛普治疗HA安全、有效。     

Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy

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核因子κB受体活化因子配体和肿瘤坏死因子α经炎性牙周膜干细胞外泌体促进破骨细胞分化

目的　慢性牙周炎表现的病理性骨吸收非常常见，牙周膜干细胞（PDLSCs）的外泌体（Exo）对骨吸收的作用和影响尚不明确，本研究分析了该Exo蛋白组分对破骨细胞分化的影响。方法　分别从正畸前拔牙患者和慢性牙周炎患者的牙周膜组织中提取PDLSCs，通过流式细胞术检测表面标记物；通过差速离心分别提取2种细胞的Exo，即Exo-WT和Exo-CP，并通过Western blot、透射电子显微镜（TEM）、蛋白浓度检测、纳米粒径追踪检测Exo特征；通过蛋白质谱检测2种Exo的蛋白组分；通过酶联免疫吸附（ELISA）验证了差异表达蛋白肿瘤坏死因子α（TNF-α）、核因子κB受体活化因子配体（RANKL）、白细胞介素（IL）-1α、转化生长因子β（TGF-β）、骨形态发生蛋白2（BMP-2）表达水平；将10、100、1 000 μg·mL^-1的Exo-CP或Exo-WT加入RAW264.7培养基中并于5 d时通过实时荧光定量聚合酶链反应（RT-qPCR）、Western blot、抗酒石酸酸性磷酸酶（TRAP）染色检测破骨分化相关指标表达情况；采用SPSS 24.0软件对实验数据进行统计学分析。结果　Exo-CP富集的差异表达蛋白主要与破骨细胞分化的TNF信号通路、核转录因子κB（NF-κB）信号通路相关；ELISA实验证实了Exo-CP中高表达TNF-α、RANKL、IL-1α，低表达TGF-β1、BMP-2（P<0.05）；Exo-CP作用于RAW264.7，显著提高了细胞的破骨分化相关基因及蛋白的表达水平，TRAP染色可见分化的破骨细胞，且呈现浓度依赖性，100、1 000 μg·mL^-1浓度Exo-CP对破骨细胞分化的促进作用显著高于10 μg·mL^-1浓度组（P<0.05）。结论　慢性牙周炎的病理性骨吸收可能由炎性PDLSCs所分泌的Exo通过促进破骨细胞分化引起，Exo中主要的作用蛋白可能为RANKL和TNF-α，本研究为慢性牙周炎骨吸收的发病机制提供了新视角。     

血液系统肿瘤患者的营养治疗专家共识

血液系统肿瘤患者诊治过程中普遍存在营养不良，化疗作为血液系统肿瘤最重要的治疗手段，进一步加剧患者的营养不 良，其最主要的原因是化疗引起的恶心、呕吐及摄食减少。诱导治疗后C反应蛋白的显著升高，提示感染发生率及炎症水平均较高， 这在一定程度上可能干扰机体代谢、加剧营养状态的恶化。血液系统肿瘤患者的营养不良表现为体质指数异常、人体成分异常、整体/ 综合评估异常和生化指标异常。血液系统肿瘤患者营养治疗的原则与其他肿瘤类似，肠内营养为主，肠外营养为辅。但是，需要注意 补充特殊营养剂：①谷氨酰胺；②针对“粒细胞减少”的饮食；③ω‐3多不饱和脂肪酸；④牛初乳及大豆饮食。通过营养筛查和评估，为 处于不同治疗阶段的血液系统肿瘤患者制定营养治疗方案，及时、恰当地进行个体化营养治疗，可显著改善血液系统肿瘤患者营养状 况、预防营养不良及相关并发症，降低治疗相关不良反应风险，提高耐受性、疗效及生活质量。     

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.     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.