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.     

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。     

益气养精法对老年肺癌患者肿瘤标志物、生存期影响研究

目的探究益气养精法对老年肺癌患者肿瘤标志物、生存期影响。方法研究纳入60例老年肺癌患者,均由本院2016年1月-2017年1月收治,采取随机数字表法将患者分为两组,对照组患者(30例)常规化疗治疗,观察组患者(30例)在化疗基础上联合益气养精法治疗,比较两组患者治疗效果、治疗前后癌胚抗原(carcino-embryonic antigen,CEA)及血清癌抗原125(serum oncoantigen 125,CA 125)肿瘤标志物水平、不良反应情况及患者2年生存率。结果观察组患治疗有效率高于对照组,P<0.05;治疗前,两组患者CEA及CA 125水平相当,P>0.05,治疗后均改善,观察组优于对照组,P<0.05;观察组患者不良反应与对照组相当,均较低,P>0.05;观察组患者2年生存率高于对照组,P<0.05。结论益气养精法治疗老年肺癌患者效果患者,患者症状改善,不良反应少,安全可靠,且患者2年生存率较高。     

Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.     

Insulin-like growth factor-1 as predictive factor of difficult laryngoscopy in patients with GH-producing pituitary adenoma: A pilot study

BackgroundGrowth hormone (GH)-producing pituitary tumors account for 10 to 15% of pituitary tumors. The hypersecretion of GH may induce changes in the airway anatomy through the activation of Insulin-like Growth factor 1(IGF-1) pathway. We sought investigate the role IGF-1 as a potential predictive factor of difficult laryngoscopy in patients with GH-producing pituitary adenoma.MethodsThis study was a single center retrospective study. We included 33 patients undergoing transsphenoidal resection of GH-producing pituitary. We recorded demographic data, el-Ganzouri risk index (EGRI) and modified Look-Evaluate-Mallampati-Obstruction-Neck mobility (mLEMON) score, and pituitary hormone plasma levels. We performed ordinal logistic regression to analyze the relationship between IGF-1 and EGRI, mLEMON, and Cormack-Lehane Grade score and a multiple logistic regression to test the capability of EGRI, mLEMON and IGF-1 levels to predict Cormack-Lehane score. Receiver operating curve (ROC), area under the curve (AUC), and cut-off value of IGF-1 were calculated.ResultsOnly 14 (42.8%) and 12 (36.36%) patients showed predictive factors of difficult intubation according to EGRI and mLEMON score, respectively. IGF-1 significantly correlated with Cormack-Lehane (p = 0.005879) but not with mLEMON and EGRI (p = 0.3080 and 0.4146, respectively). In multiple regression model IGF-1 correlated only with Cormack-Lehane grade (p = 0.0089). Area under ROC was 0.8571 and cut-off value of IGF-1 was 186.15 ng/ml.ConclusionHigher IGF-1 levels correlate with the probability of having a higher Cormack-Lehane score; classical bedside scores, such as mLEMON and EGRI, were not able to predict difficult laryngoscopy in our population.