Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

外泌体在肿瘤细胞与TAMs之间相互作用中“桥梁”和调控作用的研究进展北大核心

外泌体是一类直径为30~100 nm的圆盘囊泡,其内包含许多组分,诸如复杂RNA和蛋白质等,主要参与细胞间的信号转导。肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中普遍存在的巨噬细胞,通过对肿瘤生长、免疫逃逸、侵袭和转移、耐药性等多方面的作用影响肿瘤进程。外泌体在肿瘤相关巨噬细胞的招募、极化及抗肿瘤免疫调控等方面发挥着重要的调节功能。同时,TAMs以外泌体为媒介作用于肿瘤细胞,从而构成了外泌体、TAMs与肿瘤细胞之间相互作用的调控通路。综上所述,本文旨在阐明肿瘤细胞与TAMs之间,以外泌体为“桥梁”相互影响的潜在机制,以及靶向肿瘤细胞和TAMs来源的外泌体在恶性肿瘤治疗中的展望。     

Neutrophil-to-Lymphocyte Ratio Predicts Cancer Outcome in Locally Advanced Clear Renal Cell Carcinoma

BackgroundTo evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (ccRCC) undergoing radical nephrectomy.Material and MethodsWe retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan–Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS.ResultsAmong 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 [63.1%] male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P = .045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P = .03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4.ConclusionFor patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC.     

Giant-cell-rich tumors of bone

Neoplasms of bone with numerous non-neoplastic osteoclast type giant cells are relatively common and exhibit diverse phenotypes of the neoplastic cells. These tumors have a broad spectrum of biological potential which necessitates accurate recognition and diagnosis. Their clinicopathological features are overlapping, therefore, immunohistochemistry and molecular studies may be required for evaluation. Correlation with imaging studies provides additional information that should be incorporated into the pathological interpretation.     

右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响

目的 探讨右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响。方法 选择择期行腔镜手术治疗的老年恶性肿瘤患者90例，随机均分为3组：对照组（C组）、体温保护组（T组）和体温保护联合右美托咪定组（T-D组），每组30例。C组常规体温保护，T组和T-D组综合体温保护；T-D组麻醉诱导前10 min泵注右美托咪定0.5 μg/kg。记录3组患者麻醉诱导开始时（T₀）、手术开始30 min（T₁）、60 min（T₂）、90 min（T₃）、120 min（T₄）以及手术结束时（T₅）的鼻咽温度；于T₀、术后2 h（T₆）、24 h（T₇）和48 h（T₈）时抽取静脉血标本，测定T淋巴细胞亚群（CD3⁺、CD4⁺和CD8⁺）和自然杀伤细胞（NK cell）水平；记录患者术中麻醉药物用量及苏醒期质量指标。结果 与T₀比较，C组T₂～T₅时点鼻咽温度均明显降低（P < 0.05）；与C组比较，T组和T-D组T₂～T₅时点鼻咽温度明显升高（P < 0.05）。与T₀时点比较，C组、T组和T-D组T₆、T₇和T₈时点CD3⁺和NK cell活性均明显降低（P < 0.05）；C组在T₆、T₇和T₈时点，T组和T-D组在T₆和T₇时点，CD4⁺活性均明显降低（P < 0.05）。与C组比较，T组和T-D组T₆和T₇时点CD3⁺细胞活性均明显升高（P < 0.05）；T组在T₇时点，T-D组在T₆和T₇时点，CD4⁺细胞活性均明显升高（P < 0.05）；T组在T₇时点，T-D组在T₆、T₇和T₈时点，NK cell活性均明显升高（P < 0.05）。结论 采用体温保护措施联合右美托咪定能够维持老年恶性肿瘤患者的体温稳定，减少围手术期意外低体温（IPH）的发生，并有效提高患者苏醒期质量，减轻免疫抑制程度，加速患者早期恢复。     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis

PurposeTo evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant.Materials and MethodsThis retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques.ResultsAmong the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5–18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients.ConclusionsMW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.     

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.