【作者】 赵明；

【导师】 王新生；

【作者基本信息】 青岛大学 ， 外科学（泌尿外科）（专业学位）， 2020， 硕士

【摘要】 目的:探讨术前白蛋白碱性磷酸酶比值(albumin-to-alkaline phosphatase ratio,AAPR)与膀胱癌根治性膀胱切除术后患者总体生存期(overall survival,OS)的关系。方法:回顾性分析2007年1月至2015年12月青岛大学附属医院收治的166例膀胱癌患者的临床病理资料。收集研究对象资料包括:患者性别、年龄、体质指数(body mass index,BMI)、肿瘤大小和数目,肿瘤分期、病理分级、淋巴结转移、术前肾积水、术后辅助化疗、麻醉ASA分级、高血压、糖尿病。Cox比例风险回归模型用于评估术前AAPR与膀胱癌患者根治性膀胱切除术后总体生存期(OS)之间的关系。采用趋势性检验检测不同AAPR组间风险比(HR)变化趋势。分层分析及交互作用检验用于分析在总体样本中,各个不同因素分层下,AAPR与OS的关系。采用Kaplan-Meier法绘制生存曲线,比较不同AAPR分组间的生存率差异。广义相加模型的曲线拟合用于形象显示AAPR与OS之间的关系。结果:本队列166例患者,中位随访63个月,生存95例,死亡71例。3年生存率为61%,5年生存率为50%。术前AAPR(0.62±0.23)。单因素Cox回归分析结果显示,AAPR(HR=0.09,95%CI 0.022～0.391,P=0.001)、高AAPR组(HR=0.40,95%CI 0.216～0.742,P=0.003)、年龄(HR=2.42,95%CI 1.294～4.531,P=0.006)、肿瘤大小(HR=2.11,95%CI 1.112～4.014,P=0.023)、肿瘤数目(HR=0.62,95%Cl 0.378～1.022,P=0.061),pT3期(HR=8.93,95%CI 3.173～25.114,P<0.001)、pT4期(HR=10.39,95%CI 3.110～34.707,P<0.001)、N1期(HR=2.80,95%CI 1.422～5.531,P=0.003)、N3 期(HR=17.06,95%CI 2.192～132.863,P=0.007)、病理分级(HR=0.30,95%CI 0.113～0.817,P=0.019)、肾积水(HR=2.36,95%CI 1.406～3.939,P=0.001)、术后辅助化疗(HR=2.66,95%CI 1.674～4.247,P<0.001)与膀胱癌患者根治性膀胱切除术后总体生存期(OS)相关。调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗、BMI、肿瘤数目、病理分级后,Cox回归分析结果显示,与低AAPR组相比,高AAPR组的死亡风险降低约 59%(HR=0.406,95%CI 0.200～0.822,P=0.012),AAPR 每升高 1 个单位,死亡风险下降约80%(HR=0.199,95%CI 0.051～0.779,P=0.020)。趋势性检验结果显示,原始模型和校准模型中,AAPR不同分组间OS的HR下降趋势均有统计学意义(P=0.016),提示两者呈线性关系。分层分析及交互作用结果显示,在不同因素的分层分析下,AAPR与OS的关系与Cox结果相一致。调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗、BMI、肿瘤数目、病理分级后的曲线拟合图显示,AAPR与OS呈线性相关,随AAPR升高,术后死亡风险下降,OS延长。结论:术前AAPR与膀胱癌患者根治性膀胱切除术后OS线性相关,随术前AAPR升高,患者术后死亡风险下降,OS延长。更多还原

【Abstract】 Objective:This study investigate the relationship between preoperative albumin-to-alkaline Phosphatase Ratio and overall survival(OS)after radical cystectomy of bladder cancer.Methods:We retrospectively analyzed the clinical and follow-up date of patients with bladder cancer who underwent radical cystectomy and urinary diversion and confirmed by pathology in Department of urology surgery of Affiliated Hospital of Qingdao University from 2007.1 to 2015.12.Collecting the clinicopathologic data of 166 patients,including gender,age,body mass index(BMI),tumor size and number,tumor stage,pathological grade,lymph node metastasis,preoperative hydronephrosis,postoperative adjuvant chemotherapy,anesthesia ASA grade,hypertension and diabetes.Cox proportional hazards regression was used to evaluate the relationship between preoperative AAPR and overall survival.Trend test was used to detect the variation trend of risk ratio(HR)among different AAPR groups.Stratified analysis and interaction test were used to analyze the relationship between AAPR and OS under different factors stratified in the population sample.Survival analysis was conducted using the Kaplan-Meier method and the log-rank test to compare the survival rate differences among different AAPR groups.Curve fitting of the generalized additive model is used to show the relationship between AAPR and OS.Results:The 166 patients were followed up for 1-144 months,with a median follow-up of 63 months,71 patients died and 95 survived.The 3-year survival rate was 61%and the 5-year survival rate was 50%.The median serum AAPR level in all patients was 0.59(range:0.03-1.67).AAPR range 0.03-1.67,average 0.62±0.23.Results of univariate Cox regression model revealed that AAPR(HR=0.09,95%CI 0.022～0.391,P=0.001),high AAPR group(HR=0.40,95%CI 0.216-0.742,P=0.003),age(HR=2.42,95%CI 1.294-4.531,P=0.006),tumor size(HR=2.11,95%CI 1.112-4.014,P=0.023),pT3 stage(HR=8.93,95%CI 3.173-25.114,P<0.001),pT4 stage(HR=10.39,95%CI 3.110-34.707,P<0.001),pNi stage(HR=2.80,95%CI 1.422-5.531,P=0.003),pN3 Stage(HR=17.06,95%CI 2.192-132.863,P=0.007),pathological grade(HR=0.30,95%CI 0.113-0.817,P=0.019),hydronephrosis(HR=2.36,95%CI 1.406-3.939,P=0.001),adjuvant chemotherapy(HR=2.66,95%CI 1.674-4.247,P<0.001)were associated with OS.Compared with patients in the lowest tertile of AAPR,the risk for death of patient in the highest tertile decreased by about 59%(HR=0.406,95%CI 0.200-0.822,P=0.012)after adjustment for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy in multiple Cox regression models.Each unit increase in the AAPR was associated with about 80%decreased risk of death(HR=0.199,95%CI 0.051-0.779,P=0.020)after adjusting for the confounding variables.After adjusting for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy,the curve fitting results showed that with the increase of AAPR,the risk of death decreased and the overall survival prolonged.Consistent with the linear trend test results,the relationship between AAPR and OS is linear.Conclusions:AAPR was associated with overall survival of patients who underwent radical cystectomy of bladder cancer.With the increase of preoperative AAPR,the risk of death decreased and the OS was prolonged.更多还原