【作者】 王军梅；

【导师】 谢幸； 叶大风；

【作者基本信息】 浙江大学 ， 妇产科学， 2003， 硕士

【摘要】 背景 卵巢恶性肿瘤是女性生殖道常见的恶性肿瘤，其中绝大部分为上皮性卵巢癌(Epithelial Ovarian Cancer，简称EOC)。三分之二的EOC在初次诊断时便已是晚期，因此EOC一直是五年生存率最低的女性生殖道恶性肿瘤，迫切需要探索新的早期诊断方法。 虽然TVS(Transvaginal Sonography，简称TVS)是目前诊断EOC最有效和敏感的方法，综合文献报道诊断卵巢良/恶性肿瘤的敏感性84％-100％，特异性52％-87.1％，阳性预测值29.4％-60％，阴性预测值96％-100％，其敏感性及阴性预示值较高，但由于对低度潜在恶性肿瘤及早期EOC的低敏感性，以及鉴别良性肿块时缺乏特异性，因此迫切需要引入新的辅助技术如彩色多普勒超声。 实体肿瘤的生长、转移离不开血管生成，异常活跃的血管生成和血管结构的异常是恶性实体肿瘤的主要特征。而经阴道彩色多普勒超声(Transvaginal ColorDoppler Ultrasonography，简称TVCDU)通过对频谱进行分析可以对血管阻力、血流速度等进行定量分析，从而了解血管的血流动力学特征。但迄今TVCDU在诊断EOC中作用研究结果不一，主要表现为：(1)在众多反映血流的TVCDU参数中哪个或哪几个参数能较有效地鉴别卵巢良/恶性肿瘤尚无定论。(2)TVCDU检测肿瘤血流各个指标的分布存在明显的交叉重叠，采取什么界值鉴别卵巢良/恶性肿 浙江大学2003年硕士学位论文瘤存有不同意见。（3）迄今还没有一个理想的结合TVCDU血流参数的诊断卵巢肿瘤的评分系统。（4）目前有关TVCDU诊断卵巢肿瘤的研究中，恶性肿瘤组的样本相对较小，并且未对恶性肿瘤进行分类。 本研究的目的是通过测定60例EOC及101例良性卵巢肿块的TVCDU各血流参数，并应用免疫组化方法检测其中 116 例术后卵巢肿块内的微血管密度 （Microvessel Density，简称 MVD）状况，探讨哪几个 TVCDU指标更能反映肿瘤的血流情况，并将这些指标纳人诊断EOC的评分系统，与二维超声评分系统比较，探讨其临床应用价值。材料与方法 选择 1999年 9月工003年 2月于浙江大学医学院附属妇产科医院接受手术治疗的原发性EOC病人60例（EOC组）作为研究对象，以卵巢良性上皮性肿瘤患者36例（对照组一）、卵巢内异囊肿患者65例（对照组二）作为对照。先进行二维阴道超声检查，再用TVCDU测定卵巢肿块内血流的各项指标，包括阻力指数（Resistance Index，简称 m）、搏动指数oulsed Index，简称 PI）、收缩峰值流速／舒张末期流速oystolic Peak VelocityAliastolic End Velocity，简称 Sic）、收缩峰值速度（Peak Systolic Velocity，简称 PSV）、时间平均最大流速（T呐 AverapedMaximum Velocity，简称 TA咄V）、动脉数目、血管分布类型、舒张期有无切迹。用CD；在P免疫组化法检测卵巢肿块组织内微血管密度，并收集临床病理资料。通过比较EOC组与对照组之间TVCDU各参数的差异及分析EOC组TVCDU各参数与MVD的相关性，探讨在鉴别卵巢不同性质肿块中TVCDU各参数的准确性。并根据多因素LOgistiC回归分析结果建立彩色多普勒超声诊断EOC评分系统。以二维TVS的Depriest评分系统作对照，探讨彩色多普勒评分系统诊断EOC的准确性。结果1、TVS的 DepriCst评分系统诊断 EOC结果：EOC组评分结果为阳性 49例，阴性11例。对照组（包括对照组一和对照组H）则分别为 31例，70例。2、＊＊C组与两对照组的＊＊＊＊U各参数比较：动脉显示率、动脉数目＞3条的比例、血管分布类型、PI、RI、Sic、TAMXV差异非常显著 （功．00卜 EOC组与两 3 浙江大学2003年硕士学位论文计学意义（P＝0．193）。对照组一与二的 TVCDU各参数均无显著性差异。3、EOC组中不同分组TVCDU各参数比较：不同FIGO分期、组织类型、组织分化之间＊＊＊＊U各血流参数无统计学意义（P＞0刀5）。4、EOC组的MVD结果及与TVCDU各参数关系：EOC组与两对照组之间MVD有显著差异（P＜0．001）。对照组一与二的MV D差异无统计学意义o＞队05）。EOC组MVD与n、M、SAl呈负相关，与PSV、TAMXV无明显相关性。5、诊断EOC彩色多普勒评分系统的建立及与二维TVS的Depriest评分系统比较：肿瘤内血管分布类型、Sic值、动脉数目经多因素L呛 回归分析为独立因素，将它们纳入彩色多普勒评分系统，赋与不同分值，建立评分系统，确定6分为阈值，其诊断EOC的敏感性、特异性、阳性预示值、阴性预示值分别为88．33％、94刀6％、89．83％、93．14％，均高于二维阴道超声Depriest评分系统诊断EOC的相应值（分别为 sl．67％、69．31％、61．25％、86．42O）。结论l、应用TVCDU诊断EOC时，定性指标血管分布类型、定量指标动脉数目及血流阻力指标Sic等优于其他指标。2、以血管分布、SAl、动脉数目建立的评分系统，有助于提高TVCDU诊断EOC的准确性。以6分为阈值时，其敏感性和特异性最佳。更多还原

【Abstract】 Malignant ovarian neoplasm is a common carcinoma in female genital tract, and its prominent type is epithelial ovarian cancer (EOC). About 2/3 of HOC cases are recognized only in advanced stages with the lowest five- year survival in carcinomas of female genital tract, so it is necessary to find a new technique to diagnose early stage EOC.Transvaginal sonography (TVS) is introduced to be a major technique in diagnosis of EOC in clinical practice with sensitivities ranging from 84 to 100%, specificities from 52 to 87.1%, positive predicting values from 29.4 to 60% and negative predicting values from 96 to 100%. Because of the relatively low sensitivity in low malignant potential (LMP) tumors and early stage cancers, as well as the insufficient specificity to distinguishing benign processes, TVS has not been recommended to be widely used up to now. Nonetheless, further improvement of ultrasonographic validity using additional procedures such as color Doppler ultrasonography is desirable.Angiogenesis is an early critical step in the tumorigensis, invasion and metastasis of EOC. Abnormally active angiogenesis and malformation of vessel structure are main characters in malignant solid tumors. While color Doppler can investigate the dynamics2003characters of blood flow by quantitative analysis of resistance to vessel and blood flow velocity. So theoretically transvaginal color Doppler ultrasonography can reflect the anatomy and function of ovarian lesions, mainly the change of blood flow so as to determine the character of lesions. But there are some unresolved problems about TVCDU: (1) which parameters can effectively reflect the blood flow in ovarian lesions? (2) There are obvious overlaps of parameters between malignant and benign lesions, and what cut-off value should we take? (3) There was no scoring system combining parameters of TVCDU. Can we set up a scoring system combining parameters to improve the sensitivity and specificity of diagnosing HOC? (4) In the previous studies, the samples in malignant tumor groups were relatively small, and the malignant groups were not classified.The aim of this study is to evaluate which parameters of TVCDU can effectively reflect blood flow in tumors by measuring and comparing all kinds of parameters of TVCDU, and to set up a scoring system combining effective parameters of TVCDU, and to evaluate its clinical value on diagnosing EOC.Materials and MethodsAfter TVS examination, TVCDU was preoperatively used to determine all the parameters of blood flow in ovarian masses in 60 women with EOC, 36 with benign ovarian cystadenomas (control 1), 65 with endometriosis cysts (control 2). The parameters included resistance index (RI), pulsed index (PI), systolic peak velocity/diastolic end velocity (S/D), time averaged maximum velocity (TAMXV), number of arterioles, type of vasculature and diastolic notch. All the tissue samples were obtained after operation .Microvessel density ( MVD) was counted in the tissue samples by immunohistochemical method (SP method). And all the clinicopathologic data of cases were obtained. The parameters of TVCDU in EOC were compared with those in control groups .The correlation between MVD and the parameters in EOC group was analyzed. A color Doppler scoring system was set up by multivariate logistic regression analysis, and was evaluated on diagnosing EOC by comparing with morphological scoring system (adopting Depriest scoring system). All the data were statistically managed with SPSS 11.0 for windows. The level of P<0.05 was considered significant.Results1 、The results by Depriest scoring system on diagnosing EOC: 49 cases positive and 11 negative in EOC group, 31 positive and 70 negative in control groups (including control group 1 and 2).2、Comparison of parameters among EOC and the two control groups: There were statistical differences of arteriole showing rate, the fraction of masses with the number of arterioles more than 3,the type of vasculature, diastolic notch, PI, RI, S/D, TAMXV among EOC group and bo更多还原