【作者】 徐磊；

【导师】 王国民； 张博恒； 武睿毅；

【作者基本信息】 复旦大学 ， 泌尿外科， 2008， 硕士

【摘要】 第—部分中晚期前列腺癌患者去势术后高强度聚焦超声联合低剂量放疗的病例对照研究:生存率和并发症目的探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)联合低剂量放疗能否提高中晚期前列腺癌患者去势术后的生存率,并与全量放疗比较严重并发症的发生率。材料与方法分析中山医院(含分部)自2000年3月～至2008年4月去势手术后的中晚期前列腺癌患者117例,按照治疗方法分为HIFU联合放疗组(22例)、HIFU组(23例)、放疗组(38例)和对照组(即单纯内分泌治疗)(34例)。4组患者在年龄、初始PSA、Gleason评分和临床分期分布无显著差异。运用Stata 7.0进行统计分析,用Kaplan-Meier法计算各组生存率并绘制生存曲线,组间生存曲线比较采用Wilcoxon法,并用COX模型分别比较HIFU联合放疗组、HIFU组、放疗组与对照组的生存率差异;Wilcoxon法比较HIFU联合低剂量放疗与联合全量放疗的组间生存曲线以及HIFU作为补充治疗与作为补救治疗的组间生存曲线;秩和检验比较HIFU联合低剂量放疗与联合全量放疗以及放疗组的并发症发生率。结果①HIFU联合放疗组、HIFU组、放疗组和对照组3年总体生存率分别为100%、63.84%、73.58%和48.56%,HIFU联合放疗组与对照组有显著差异(P=0.029),其余2组与对照组总体生存率无显著差异,4组间总体生存曲线Wilcoxon检验存在显著差异(P=0.024);4组的3年疾病特异生存率分别为100%、63.84%、75.74%和54.27%,HIFU联合放疗组与对照组有显著差异(P=0.026),其余2组与对照组疾病特异生存率无显著差异,4组间疾病特异生存曲线Wilcoxon检验存在显著差异(P=0.014)。②HIFU联合低剂量放疗与联合全量放疗在总体生存率(P=0.382)和疾病特异生存率均无显著差异(P=0.677)。③秩和检验HIFU联合/不联合低剂量放疗较HIFU联合全量放疗和全量放疗Ⅱ级或以上严重并发症发生率显著减少(泌尿生殖系并发症P=0.012,消化道并发症P=0.011)。④HIFU作为补充治疗较补救治疗显著提高中晚期前列腺癌患者的总体生存率(P=0.033)和疾病特异生存(P=0.038)。⑤HIFU作为补充治疗的患者在平均5.40±3.33月后使PSA降到最低值平均0.56±0.78ng/mL,且较单纯内分泌治疗在更短的时间(P=0.036)使PSA降到最低值。结论中晚期前列腺癌患者在去势术后给予HIFU联合低剂量放疗作为补充治疗可以显著提高总体生存率和疾病特异生存率,并能显著降低放疗严重并发症的发生率,从而改善生活质量,为中晚期前列腺癌提供了一种安全、有效的治疗方法。第二部分中晚期前列腺癌患者高强度聚焦超声治疗前后机体免疫功能变化的初步观察目的探讨HIFU对中晚期前列腺癌的抗肿瘤免疫作用。材料与方法将中晚期前列腺癌患者随机分为2组,HIFU组行单纯HIFU治疗11例(所有患者均已在入组前行去势手术治疗),对照组行单纯去势手术10例。分别于治疗前和治疗后抽取静脉血5ml,两次抽血时间间隔约4周。检测CD19~+、肿瘤坏死因子-α、CD4+CD25+Foxp3+调节性T细胞、VEGF、TGF-β1、IFN-γ和IL-2。HIFU组HIFU治疗前后对照、对照组去势术前后对照以及HIFU组与对照组治疗前后差值对照均采用Kruskal-Wallis秩和检验,取P＜0.05有统计学差异。应用Stata 7.0软件。结果HIFU组患者HIFU治疗后肿瘤坏死因子-α(P=0.033)和TGF-β1(P=0.046)显著降低,余指标无显著变化;对照组患者去势术后CD4+CD25+Foxp3+调节性T细胞显著上升(P=0.023),余指标无显著变化;HIFU组治疗前后差值较对照组治疗前后差值CD19~+(P=0.005)、IFN-γ(P=0.012)和IL-2(P=0.007)显著上升,肿瘤坏死因子-α(P=0.029)、CD4+CD25+Foxp3+调节性T细胞(P=0.001)、VEGF(P=0.016)和TGF-β1(P=0.027)显著降低。结论中晚期前列腺癌患者去势术后机体抗肿瘤免疫受到抑制,而HIFU治疗可以有效提高患者抗肿瘤免疫作用,其机制可能通过降低机体免疫抑制,分泌免疫促进因子和提高体液免疫等。更多还原

【Abstract】 PartⅠHifu associated Low Dose Raditation in Intermediate and Advanced Prostate Cancer Patients,A case control study:survival rates and morbiditiesObjectives:to observe the survival rates after high intensity focused ultrasound(HIFU) associtated with low-dose radiation in the treatment of intermediate and advanced prostate cancer and compare the severe mordity rates with conventional-dose radiation.Material and methods:We evaluated the records of 117 patients of intermediate and advanced prostate cancer in the Fudan University Zhongshan Hospital Prostate Cancer Database who had had surgical castration from 2000.3～2008.4.All patients were separated into 4 groups according the therapy,HIFU associated radiation Group (22cases),HIFU Group(23 cases),radiation Group(38cases)和control Group(single hormone therapy)(34cases).Patients of 4 groups had no significant disparity in age,initial PSA,Gleason sum and clinical stage.Statistical analysis were performed with Stata,version 7.0.to evaluate the survival rates and draw the survival curve by Kaplan-Meier method,to compare the survival curves among groups by Wilcoxon,to compare the survival rates of other 3 groups with the control group with Cox model, to compare the survival curve betweent HIFU associated with low-dose and convetional-dose radiation.To compare the survival curve between HIFU as the supplementary treatment and as salvage treatment,and to compare mordity rates among HIFU associated with low-dose radiation,HIFU associated with conventional radiation and single conventional radiation by rank-sum test.Results:①the 3-year overall suvvival rates of HIFU associate with radiation Group,HIFU Group,Radiation Group and Control Group are 100%、63.84%、73.58%and 48.56%,respectively.There had a significant disparity between HIFU associate with radition and Control Group(P=0.029),other 2 groups had no signicant disparity with Control Group.Overalsurvival curve among the 4 groups had significantdisparity (P=0.024).the 3-year disease-specific suvvival rates of HIFU associate with radiation Group,HIFU Group,Radiation Group and Control Group are 100%、63.84%, 75.74%and 54.27%,respectively.There had a significant disparity between HIFU associate with radition and Control Group(P=0.026),other 2 groups had no signicant disparity with Control Group.Disease-specific survival curve among the 4 groups had significantdisparity(P=0.014).②There had no significant disparity in overall survival rate(P=0.382) and disease-specific survival rate(P=0.677)between HIFU associate with low-dose and conventional radiation.③HIFU associate with low-dose radiation significantly decrease the sever mordity rates compared with HIFU associate with conventional radiation and single Conventional radiation(GU morbidity P=0.012,GI morbidityy P=0.011).④HIFU as supplementary therapy could significantly improve the overall survival(P=0.033) and disease-specific survival (P=0.038) rate over as salvage therapy.⑤Patients in the treatment of HIFU as supplementary therapy had a mean PSA nadir of 0.56±0.78ng/mL after mean time of 5.40±3.33 moths,and the time to nadir is shorter than single hormone therapy(control group)(P=0.036).Conclusion:HIFU associate with low-dose radiation as a supplementary treatment in the intermediate and advanced prostate cancer patients after surgical castration could significantly improve their overall survival and disease-specific survival rates,decrease the radiation related severe morbidity and then improve the survival quality.This provided a safe and effective treatment for intermediate and advanced prostate cancer. PartⅡInitial Oberservation on Body Immunity Change in the Intermediate and Advanced Prostate Cancer Patients after HIFUObjective:to investigate the anti-tumor immunity by HIFU on intermediate and advanced prostate cancer.Material and Methods:Randomly separate intermediate and advanced prostate cancer patients into 2 groups,HIFU treatment 11cases(HIFU group,all patients had the surgical castration before entrance),single surgical castration 10 cases (control group).To evaluate their CD19+ TNF-α,CD4+CD25+Foxp3+Treg Cell,VEGF, TGF-β1,IFN-γand IL-2 before and after treatment,about 4 weeks of interval. to compare the disparity by rank-sum test.Results:Patients of HIFU group had a significant decrease in TNF-α(P=0.033) and TGF-β1(P=0.046) after HIFU;patients of control group had a significant increase in CD4+CD25+Foxp3+Treg Cell;compared with difference after surgical castration in control group,difference after HIFU in HIFU group had a signicant increase in CD19~+ (P=0.005),IFN-γ(P=0.012) and IL-2(P=0.007),a significant decrease in CD4+CD25+Foxp3+Treg Cell(P=0.001),VEGF(P=0.016) and TGF-β1(P=0.027).Conclusion:Patients of intermediate and advanced prostate cancer had a immune depression after surgical castration;HIFU could effectively increase their anti-tumor immunity,by decreasing the body immune depression,secreting immune enhancing factor and increasing humoral immunity.更多还原