早期子宫内膜癌和重度不典型增生保留生育功能治疗的妊娠结局分析

发布时间：2018-05-12 06:23

本文选题：子宫内膜癌 + 子宫内膜重度不典型增生　；参考：《北京协和医学院》2016年博士论文

【摘要】：背景和目的约3%～14%的子宫内膜腺癌患者发病年龄在40岁以下,其中70%～85%尚未生育。迄今保守治疗早期子宫内膜癌的报道多为小样本临床观察,多数仅针对肿瘤疗效进行研究,尚无预测保留生育功能妊娠结局的相关指标。本研究希望明确保留生育功能治疗早期子宫内膜腺癌及重度不典型增生的治疗效果、为预测妊娠结局提供相关指标。对象和方法总结国内外对孕激素治疗早期子宫内膜癌的现状,对其进行系统回顾和荟萃分析,评价疗效和安全性。回顾研究北京协和医院20年来采用保留生育功能治疗早期子宫内膜腺癌及重度不典型增生共95例患者的临床资料,分析其治疗效果、妊娠结局及相关因素,初步探究HOX A10、APOD、SCD、LEPR、SREBP1、FASN等分子标记物在这些病变中的表达情况及其与妊娠的关系。并通过对妊娠相关因素的分析,构建logistic回归模型预测妊娠结局。结果荟萃分析中纳入25篇文章共445名患者。基于随机效应模型,患者对孕激素的反应率为82.4%,复发率25.0%,妊娠率28.8%,活产率19.6%。体重增加、肝功能异常以及凝血试验异常是最常见的治疗相关副反应。2例患者在随访时出现疾病相关死亡。纳入49例具有生育意愿及生育结局的早期子宫内膜癌和重度不典型增生患者,平均年龄29.3±3.5岁。全部获得病理CR,中位CR时间6个月。50.0%患者成功妊娠,34.7%患者最终成功获得活产儿,活产率为70.8%。平均随访62.5±41.7个月,57.1%复发,平均复发时间为21.9±18.9个月。发病前是否合并不孕、治疗前内膜厚度与妊娠结局相关。HOX A10在肿瘤组织中低表达,成功妊娠患者治疗中内膜间质中HOX A10的表达量显著高于未妊娠者。APOD、SCD、LEPR、SREBP1和FASN在肿瘤组织中表达阳性率普遍较高,差异无统计学意义。建立logistic回归模型,分析不孕、内膜厚度、HOX A10表达及BMI与妊娠结局的关系,各参数P0.05,没有统计学意义。经输入法强制回归建立的模型其准确性可,但稳定性一般。结论本课题总结了国内外多个中心的针对保留生育功能治疗早期子宫内膜癌和重度不典型增生的系统研究,获得了满意的缓解率。在较高的完全缓解率的基础上,能否妊娠成为了保守治疗的一个重要预后指标。HOX A10的高表达可以作为判断妊娠结局的重要指标。构建数学模型预测妊娠结局的方法虽然尚不成熟,但其具有全方面评估患者生殖状态的优势,可为预测妊娠及患者筛选提供依据。
[Abstract]:Background and objective about 34% of patients with endometrial adenocarcinoma are under 40 years old, of whom 70% have not yet given birth. Up to now, the reports of conservative treatment of early endometrial carcinoma are mostly small sample clinical observation, and most of them only focus on the curative effect of tumor, and there is no related index to predict pregnancy outcome of preserving fertility function. The purpose of this study was to determine the therapeutic effect of preserving reproductive function on early endometrial adenocarcinoma and severe atypical hyperplasia, and to provide relevant indicators for predicting pregnancy outcome. Objects and methods the present situation of progesterone in the treatment of early endometrial carcinoma was summarized, and its efficacy and safety were evaluated by systematic review and meta-analysis. The clinical data of 95 patients with early endometrial adenocarcinoma and severe atypical hyperplasia treated by preserving fertility in Beijing Union Hospital in the past 20 years were retrospectively studied, and the therapeutic effect, pregnancy outcome and related factors were analyzed. To investigate the expression of HOX A10 APODN and its relationship with pregnancy. Logistic regression model was constructed to predict pregnancy outcome by analyzing the related factors of pregnancy. Results A total of 445 patients were included in 25 articles in the meta-analysis. Based on the random effect model, the response rate of patients to progesterone was 82.4, the recurrence rate was 25.0, the pregnancy rate was 28.8and the live birth rate was 19.6B. Weight gain, abnormal liver function and abnormal coagulation test were the most common treatment-related side effects in 2 patients with disease-related death at follow-up. 49 patients with early endometrial carcinoma and severe atypical hyperplasia with fertility intention and outcome were enrolled, with an average age of 29.3 卤3.5 years. Pathological CRs were obtained in all patients. The median CR time was 6 months. 50.0% of the patients were successful in pregnancy. 34.7% of the patients finally succeeded in obtaining live infants, and the live birth rate was 70.8%. The mean follow-up time was 62.5 卤41.7 months (57.1%) and the mean recurrence time was 21.9 卤18.9 months. The thickness of endometrium before treatment was related to pregnancy outcome. HOX A10 expression was low in tumor tissue. The expression of HOX A10 in endometrial stroma was significantly higher in successful pregnancy patients than that in unpregnant women. The positive rate of HOX A10 expression in tumor tissues was significantly higher than that in unpregnant women (P < 0.05). Logistic regression model was established to analyze the expression of HOXA10 in infertility, intimal thickness and the relationship between BMI and pregnancy outcome. The parameters were not statistically significant (P 0.05). The model established by forced regression by input method is accurate, but stable. Conclusion the systematic study on the treatment of early endometrial carcinoma and severe atypical hyperplasia by reserving fertility function in many centers at home and abroad has been summarized, and the satisfactory remission rate has been obtained. On the basis of high complete remission rate, whether pregnancy becomes an important prognostic index of conservative therapy. The high expression of HOX A10 can be used as an important indicator to judge the outcome of pregnancy. Although the mathematical model for predicting pregnancy outcome is not mature, it has the advantage of evaluating the reproductive status of patients in all aspects, which can provide the basis for predicting pregnancy and screening of patients.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.33;R711.74

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