骨肉瘤组织中血管生成拟态的表现及预后意义

目的 探讨骨肉瘤组织中血管生成拟态（VM）的存在情况及其与临床病理特征和预后的关系。方法 收集骨肉瘤标本66例,采用CD34和PAS双重染色方法检测骨肉瘤组织中VM存在情况,探讨骨肉瘤VM与临床病理特征和预后的相关性以及VM与黏着斑激酶（FAK）、迁移诱导基因（Mig）-7表达的关系。结果 66例骨肉瘤中存在15例VM,阳性率为22.7％。骨肉瘤VM与患者性别、年龄、肿瘤直径、肿瘤部位、术式及术前化疗坏死率无关。VM（+）组FAK及Mig-7的阳性表达率均高于VM（-）组。VM（+）组患者的总生存期和无转移生存期均短于VM（-）组患者（P＜0.05）,Cox风险比例回归模型显示VM和术前化疗效果是预测骨肉瘤生存期和发生转移的两个独立预后因素。结论 VM存在于骨肉瘤组织中并且是其重要的预后指标,FAK及Mig-7与骨肉瘤VM的形成有密切关系。     

睾丸生殖细胞恶性肿瘤血管生成拟态的研究和预后相关性分析*

目的:研究睾丸生殖细胞恶性肿瘤（Testicular germ cell malignant tumors ,TGCMT）中是否存在血管生成拟态（Vasculogenic mimicry ,VM）,阐述血管生成拟态的临床意义及相关机制。方法:收集TGCMT组织切片40例临床和预后资料完整,复习切片明确诊断后进行CD34和PAS 双重染色,证实肿瘤组织中VM的结构,利用多因素性相关分析阐述VM的临床意义。结果:40例睾丸生殖细胞恶性肿瘤中VM阳性者22例（53.66％）。 χ2检验分析血管生成拟态的阳性率与肿瘤大小、有无转移以及患者的生存状态之间具有差异,P=0.013,P=0.045,P=0.000。Ka?plan-Meier 生存分析显示有无VM肿瘤患者生存时间差异具有统计学意义,根据Log-rank 检验法比较两组间生存曲线有显著性差异（P=0.012 7）。 Cox 比例风险模型分析表明VM是影响TGCMT患者预后的危险因素（P=0.038,OR= 4.043）。结论:TGCMT中存在VM,VM是影响TGCMT患者预后的危险因素。      

胃肠道间质瘤中血管生成拟态初步研究

目的：研究胃肠道间质瘤中是否存在血管生成拟态及临床意义.方法：收集84例CIST标本及临床病理资料．CD31／PAS双重染色结合CD117、CD31免疫组化染色证实VM存在，分析VM与患者临床病理指标之间的关系结果：84例GIST中21例具有VM；核分裂数≥5个／50HPF组和〈5个／50HPF组和有无肝转移组间VM阳性率差别有统计学意义（P=0．000，0．008）。极低危／低危组、中危组和高危组三组VM阳性率分别为5．9%，12．5％，39.5％，三组之间VM阳性率差异有统计学意义（P=0．010，0．020）Kaplan—Meier生存分析提示有VM组和无VM组生存时间差异有统计学意义（P=0．0000）.Cox比例风险模型分析表明有VM、肿瘤大小≥10cm和出血是影响GIST患者预后的危险因素（P=-0．000．0．005，0．032）=结论：GIST中存在VM，VM是影响GIST患者预后的不利因素，有VM的患者易发生肝转移．预后比无VM的患者差、     

PTEN 基因表达在ⅡB期骨肉瘤生存分析中的意义

目的 分析Ⅱ B期肢体骨肉瘤预后的相关因素,评价PTEN在Ⅱ B期骨肉瘤生存分析中的意义.方法 收集1996～2001年Ⅱ B期肢体骨肉瘤资料完整病例标本64例,男38例,女26例,平均年龄21.4(7～52)岁.发病部位:肱骨近端10例,股骨远端28例,股骨近端3例,胫骨近端23例.收集患者年龄、性别、组织分型,是否保肢治疗、是否术前化疗、是否规律化疗、肿瘤大小等临床相关因素.所有患者标本进行PTEN免疫组织化学研究,多因素统计生存分析.结果 64例骨肉瘤患者中复发11例,其中截肢患者中仅1例复发,占4.17%;保肢患者中10例复发,占25%,差异有统计学意义(P＜0.05).规律化疗组38例中3例复发,占7.89%,非规律化疗组26例中8例复发,占30.76%,差异有统计学意义(P＜0.05).64例骨肉瘤患者中肺转移29例,PTEN表达与肺转移相关(P=0.001).规律化疗组38例中11例复发,占28.94%;非规律化疗组26例中18例复发,占69.23%,,差异有统计学意义(P＜0.01).Cox模型分析肿瘤体积大是危险因素,而规律化疗和PTEN免疫染色阳性是保护因素.Keplan-Meier分析骨肉瘤患者PTEN阳性和规律化疗者生存期长.结论 PTEN染色阳性是骨肉瘤患者预后的保护性因素,规律化疗是改善肢体骨肉瘤患者预后的关键.     

PKM2表达和巨噬细胞中CD163升高协同促进骨肉瘤进展

目的 探讨骨肉瘤中PKM2与相关病理学特征的关系,以进一步寻找判断骨肉瘤预后的标志物。方法 收集原发性骨肉瘤石蜡包埋标本88例,并对标本进行组织微阵列构建,免疫组织化学法检测PKM2的表达情况, Kaplan-Meier分析预后价值,Cox回归模型进行参数与患者预后的相关性分析。结果 M2巨噬细胞特异性标志物CD163在骨肉瘤基质中升高,PKM2过表达与M2巨噬细胞浸润在骨肉瘤中呈正相关。结论 PKM2过表达和M2巨噬细胞浸润是骨肉瘤患者预后不良的因素。     

局部复发性骨肉瘤56例患者的预后因素分析

目的:探讨影响局部复发性骨肉瘤患者预后的相关因素.方法:2002年1月-2009年12月本科共收治并确诊骨肉瘤患者339例,回顾性分析其中56例局部复发性骨肉瘤患者的临床资料,并对其预后进行随访,随访时间为13～130个月,平均45.1个月.以性别、年龄、肿瘤部位、肿瘤大小、手术方式、新辅助化疗、第1次术后辅助化疗次数、肺转移、其他部位远处转移和局部复发后治疗这10项因素作为变量,应用Kaplan-Meier法计算患者总生存率和复发后生存率,应用log-rank检验进行预后的单因素分析,应用COX回归模型进行预后的多因素分析.结果:56例局部复发性骨肉瘤患者局部复发后的中位生存时间29个月(95％可信区间:24.5～33.5),总的中位生存时间为51个月(95％可信区间:29.3～72.7),累计2年和3年生存率分别为78.6％和46.4％.单因素分析显示,性别、肿瘤大小、肺以外其他部位转移和局部复发后治疗方案是局部复发性骨肉瘤的预后因素(P＜0.05);多因素分析显示,肺以外其他部位转移和局部复发后治疗方案是影响预后的独立相关因素(P＜0.05).年龄、肿瘤部位、手术方式、新辅助化疗、第1次术后辅助化疗和肺转移与复发性骨肉瘤的预后无关(P＞0.05).结论:肺以外其他部位转移和局部复发后治疗是影响局部复发性骨肉瘤患者预后的独立影响因素,对局部复发灶和远处转移灶采用积极的外科治疗能够有效地提高局部复发性骨肉瘤患者的生存率.     

32例颌面部骨肉瘤临床特点比较及预后影响因素分析

背景与目的：骨肉瘤是较常发生于青少年的间叶组织来源的恶性肿瘤。多发于四肢，较少发生于颌面部。此类骨肉瘤的治疗大多为手术切除，辅以化疗和放疗。因为较为罕见，国内报道较少。故该研究探讨影响颌面部骨肉瘤预后的相关因素。方法：回顾性分析了2010年1月—2017年1月收治的32例颌面部骨肉瘤的临床病理资料并且对预后进行随访，随访时间为7~90个月，平均为75个月，以性别、年龄、肿瘤大小、手术切缘、肿瘤的生长部位、手术方式、手术后进行辅助化疗的次数、局部复发及转移这9项因素作为变量。应用Kaplan-Meier计算并分析其生存率，应用log-rank进行单因素分析检验，应用Cox回归模型进行多因素分析，研究这些因素和患者的生存率之间的关联。结果：32例骨肉瘤患者中位总生存期(overall survival，OS)为(47.6±8.4)个月(95%CI：31.1~64.1)，累计1年和2年生存率分别为84%和72%，5年生存率为44%。单因素分析结果显示，骨肉瘤的手术切缘、术后化疗与患者的复发有关。肿瘤直径、手术切缘、术后辅助化疗是影响骨肉瘤生存的因素。多因素分析结果显示，肿瘤大小、术后辅助化疗是影响颌面部骨肉瘤患者治疗预后的主要因素。其他变量差异无统计学意义。结论：颌面部骨肉瘤有独特的生物学特性和预后，手术切缘和术后辅助化疗次数是影响骨肉瘤患者预后的主要因素。     

HER2基因表达与骨肉瘤预后

目的:研究骨肉瘤中HER2基因的表达与临床预后的关系。方法:对82例骨肉瘤患者的临床病理资料进行回顾性研究,应用HER2单克隆抗体对组织切片进行免疫组织化学染色,并将上述资料与患者的预后进行分析。结果:骨肉瘤患者HER2表达与患者预后相关(P<0.05),HER2高表达的骨肉瘤患者预后较差。结论:HER2检测是骨肉瘤预后判断的一项有价值的指标;同时,HER2为骨肉瘤的治疗提供一种可能的生物靶点。     

骨肉瘤组织CRM1基因表达预后意义的分析

目的:分析CRM1基因在骨肉瘤手术标本中的表达及其预后价值.方法:采用蛋白质印迹法检测57例骨肉瘤手术标本和5例正常软骨组织标本中的CRM1基因表达,并进一步分析其对于骨肉瘤患者的预后价值.结果:CRM1基因在骨肉瘤组织中的表达显著高于在正常组织中的表达;CRM1基因高表达和血清碱性磷酸酶水平升高显著相关(P=0.001),但和血清乳酸脱氢酶水平升高无关(P=0.065).单因素分析表明,CRM1基因高表达和肿瘤大小以及病理学分级之间显著相关(P值分别为0.014和0.003),而和其他临床病理特点无关.Kaplan-Meier生存分析表明,CRM1基因高表达对于骨肉瘤患者的无进展生存期和总生存期差异有统计学意义(P值分别为0.016和0.008).而多因素分析表明,CRM1基因高表达对于骨肉瘤患者是一个独立预后因素(95%CI, 1.27～5.39).结论:CRM1基因高表达与骨肉瘤患者的血清碱性磷酸酶水平升高、肿瘤大小以及病理学分级显著相关;是骨肉瘤的独立预后因素.     

59例青少年及儿童骨肉瘤患儿远期预后影响因素分析

目的探讨59例青少年及儿童骨肉瘤患儿远期预后影响因素。方法选择59例青少年及儿童骨肉瘤患儿,所有患儿均给予手术及术后辅助化疗,采用Kplan-Meier法对患儿的术后总生存率进行计算,采用单因素分析法对随访资料进行分析,采用Cox比例风险回归模型行多因素分析。结果 59例患儿中,术后3年患儿生存41例,死亡18例,生存率为69. 5%(41/59)。单因素分析结果表明,KPS评分、Enneeking分期、辅助化疗次数与青少年和儿童骨肉瘤患儿的远期预后相关,而性别、年龄、肿瘤部位、肿瘤大小、病理性骨折、肿瘤类型、手术类型与青少年和儿童骨肉瘤的远期预后无关。多因素分析结果表明,KPS评分、Enneeking分期、辅助化疗次数是影响青少年和儿童骨肉瘤的远期预后的独立相关影响因素。结论规范的辅助化疗可提高患儿的生存率,KPS评分、Enneeking分期是影响青少年、儿童骨肉瘤预后的独立危险因素。     

横纹肌肉瘤患者列线图预后模型的构建

  目的  构建列线图预测横纹肌肉瘤患者的1、3、5年生存率。  方法  从美国国立癌症研究所的监测、流行病学、结果数据库（SEER）数据库中收集1975年至2016年间诊断的横纹肌肉瘤患者,经筛选后最终获得861例符合条件的患者,采用单因素Kaplan-Meier法及多因素Cox模型分析确定横纹肌肉瘤患者独立的预后影响因素,然后将这些因素纳入并构建预测横纹肌肉瘤患者1、3、5年生存率的列线图。通过一致性指数（C-index）对所得列线图进行内部验证,检查其预测精度;同时,列线图预后模型的校正曲线一致性良好。  结果  年龄、病理类型、病理分级、总分期、手术、放疗及化疗均是横纹肌肉瘤患者的独立预后影响因素（P < 0.05）,将这些因素纳入并成功构建了列线图。列线图的内部验证所得C指数为0.776。  结论  本次研究构建的横纹肌肉瘤患者生存风险的列线图具有良好的预测精度,有助于临床医师对横纹肌肉瘤患者预后作出较为准确的评估,也有利于对横纹肌肉瘤患者实施个体化诊疗。      

肺腺癌患者列线图预后模型的构建与验证

目的 基于SEER数据库的大样本数据,构建肺腺癌患者生存预后的列线图预测模型.方法 回顾性分析SEER数据库收集的2010—2015年诊断为肺腺癌患者的临床数据.根据影响肺腺癌患者预后的独立因素,采用Lasso Cox回归分析构建列线图模型.C指数和校准曲线评估列线图的判别和校准能力.使用NRI和DCA曲线评估列线图的...     

局限期可手术食管癌术前放化疗预后因素分析及生存预测模型

目的 利用SEER数据库分析局限期可手术食管癌术前放化疗患者的预后及其相关因素,并建立生存预测列线图,为筛选术前放化疗患者提供一定参考。方法 选取SEER数据库2010-2015年食管癌接受术前放化疗且分期为T1b-4aN0-3M0(2010年AJCC第7版分期)的病例;生存率采用Kaplan-Meier法,单因素分析采用Logrank检验,多因素分析采用Cox模型检验;通过R软件建立预测模型列线图;一致性指数(C-index)及校准曲线用来评价模型准确度。结果 共1697例患者符合条件并可纳入分析。单因素分析显示性别、T分期、N分期、分化程度与总生存(OS)及癌症特异生存(CSS)均相关(P均<0.001),年龄与OS相关(P=0.027)。多因素分析显示年龄、性别、分化程度、N分期与OS相关;性别、分化程度、T分期、N分期与CSS相关(P均<0.05)。将预后相关因素纳入Nomogram预后模型,5年OS、CSS的C-index值分别为0.60、0.61。同样方法建立食管鳞癌亚组患者预后模型,OS及CSS的C-index值为0.62、0.64。结论 性别、临床分期、分化程度为局限期可手术食管癌行术前放化疗者CSS预后因素,根据以上数据建立的列线图可为是否采用术前放化疗联合手术治疗这一模式提供一定参考。     

Development and validation of a new clinical staging system to predict survival for esophageal squamous cell carcinoma patients: Application of the nomogram

IntroductionSurvival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC).Materials and methodsOn the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores.ResultsOn multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories.ConclusionsThe risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.     

Prognostic stratification based on a novel nomogram for left-sided pancreatic adenocarcinoma after surgical resection: a multi-center study

Left-sided pancreatic adenocarcinoma (LPAC) has a poorer prognosis and has some distinct features compared to cancer of pancreatic head. A reliable model to predict the prognosis of LPAC following surgery is needed in clinical practice. Our study included 231 patients with resected LPAC from 3 Chinese pancreatic disease centers. Cox-regression analysis was conducted to identify independent risk factors of LAPC. Then we established a nomogram and performed C-index, receiver operating characteristic curve, calibration plot and decision curve analysis to assess its discrimination and calibration. As a result, CA19-9, surgical margin, tumor differentiation, lymph node metastasis, and postoperative adjuvant chemotherapy were identified as significant prognostic factors. Based on these predictors, a novel nomogram was constructed. The nomogram achieved high C-indexes in the training cohort (0.805) and validation cohort (0.719), which were superior than the AJCC-8 staging system and other nomograms. The area under curve of the nomogram for predicting patients survival at 1-, 2-, and 3-year in training cohort were more than 0.8. Kaplan-Meier survival curve for the subgroups stratified based on the nomogram showed a better separation than the AJCC-8 stage I, II, III, indicating a superior ability of risk stratification for our model. In summary, we constructed a nomogram which showed a better predictive ability for patients’ survival with LPAC after surgical resection than the AJCC staging system and other predictive models. Our model would be helpful to discriminate high-risk LPAC and facilitate clinical decision making.     

老年营养风险指数对根治性放化疗食管鳞癌患者长期生存的预测价值

  目的  探讨老年营养风险指数（geriatric nutritional risk index,GNRI）对接受根治性放化疗（definitive chemoradiotherapy,dCRT）的食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）患者长期生存的预测价值。  方法  共收集2013年1月至2015年12月期间202例在河北医科大学第四医院接受根治性放化疗ESCC患者的临床资料。计算放疗前1周内患者GNRI和预后营养指数（prognostic nutritional index,PNI）,将患者分为高GNRI组（GNRI≥98）和低GNRI组（GNRI<98）。回顾性分析GNRI对无进展生存（progression-free survival,PFS）和总生存（overall survival, OS）的影响。利用R软件建立列线图预测模型,以一致性指数（C-index）和校准曲线评估模型准确度,进一步探索GNRI和N分期、GNRI和PNI联合指标的预后预测价值。  结果  202例患者中,高GNRI组145例（71.8%）,低GNRI组57例（28.2%）。多因素分析显示,N分期、放疗剂量和GNRI是PFS和OS的独立预后因素。根据预后因素分别建立PFS和OS的列线图模型,C-index分别是0.663,0.656,1,3,5年PFS和OS的校准图显示出预测值与实际值具有较好的一致性。将GNRI和N分期联合、GNRI和PNI联合分析时,发现两项指标较单纯GNRI相比,其预测预后生存的精确度显著增加（GNRI、coGNRI-N、coGNRI-PNI的AUROCs=0.628、0.657、0.694）。  结论  GNRI可作为根治性放化疗食管鳞癌患者生存的一个简便高效的预测指标。GNRI联合N分期与GNRI联合PNI可提高预测准确性。      

Development and External Validation of a Clinical Nomogram for Individually Predicting Survival of Metaplastic Breast Cancer

BackgroundFew studies have concerned the prognosis of metaplastic breast cancer (MpBC), a rare and diverse malignancy. A prognostic index estimating the MpBC survival would be attractive in clinical practice.Patients and MethodsWe retrospectively analyzed MpBC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors were identified and the final nomogram was developed to predict the 1-, 3-, or 5-year overall survival (OS). Calibration curves were provided to internally validate the performance of the nomogram and discriminative ability was appraised by concordance index (C-index).ResultsA total of 1017 MpBC patients diagnosed between 2010 and 2015 were assigned into 3:1 as training set (n = 763) and SEER validation set (n = 254). An external validation was performed by an individual set of 94 MpBC patients from National Cancer Center in China from 2010 to 2018. The nomogram finally consisted of 7 independent prognostic factors and presented a good accuracy for predicting the OS with the C-index of 0.77 (95% CI: 0.751-0.786). Interestingly, the nomogram based on the western (including 92.5% non-Asian) SEER validation population (C-index of nomogram: 0.76, 95% CI: 0.737-0.796) also has an optimal discrimination in Asian population (C-index of nomogram: 0.70). The calibration plots of the nomogram predictions were also accurate and corresponded closely with the actual survival rates.ConclusionThis novel nomogram was accurate enough to predict the OS by using readily available clinicopathologic factors in MpBC general population, which could provide individualized recommendations for patients and clinical decisions for physicians.     

Nomogram predicted disease free survival for colorectal liver metastasis patients with preoperative chemotherapy followed by hepatic resection

BackgroundHepatic resection is regarded to as a potentially curative option for colorectal cancer liver metastases (CRLM), but it is associated with a high rate of recurrence. The present study intended to establish an effective nomogram to predict disease free survival (DFS) and select candidates of hepatic resection.MethodsThe nomogram was based on a retrospective study on 447 CRLM patients treated with preoperative chemotherapy followed by hepatic resection using a multicentric database between January 1st, 2010 and December 31st, 2017. Results were validated using bootstrap resampling on 117 patients. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. Overall survival, disease free survival, and local recurrence rate for patients with colorectal cancer were measured.ResultsBased on multivariate analysis of the primary cohort, independent factors for DFS included tumor size larger than 5 cm, multiple liver metastases(>1), RAS mutation, primary lymph node metastasis and tumor size increase after preoperative chemotherapy. These five factors were all considered in the nomogram. The C-index of the nomogram for predicting survival was 0.675. With external validation, the C-index of the nomogram for the prediction of the DFS was 0.77, which demonstrated that this model has a good level of discriminative ability. For the 382 patients (66.7%) who developed recurrence, the optimal cutoff point for early recurrence was determined to be 12 months after hepatic resection.ConclusionsThe proposed nomogram demonstrated accurate prognostic prediction of DFS for CRLM patients with preoperative chemotherapy followed by hepatic resection.