保留生育功能治疗效果中的作用

Effects of pathological assessment of endometrial tissue in fertility-sparing treatment with progestin for endometrial carcinoma of stage Ⅰa and complex atypical hyperplasia

目的对Ⅰa期子宫内膜样腺癌及子宫内膜复杂性不典型增生患者应用孕激素治疗的临床病理学变化及预后进行观察，探讨子宫内膜病理检查在孕激素治疗效果评估中的作用。方法对2004年11月至2011年11月浙江大学医学院附属妇产科医院收治的40岁以下有强烈保留生育功能意愿的9例Ⅰa期子宫内膜样腺癌及21例子宫内膜复杂性不典型增生患者应用孕激素治疗，连续用药6～9个月，每3个月进行1次病理疗效评估，病理观察肿瘤性病变消退、变化情况以及子宫内膜对孕激素治疗的反应情况；并长期随访观察。结果（1）用药6。9个月内9例子宫内膜样腺癌及21例子宫内膜复杂性不典型增生患者中，分别有5例（5／9）、18例（86％，18／21）达到完全反应（癌及癌前病变完全消退），2例、2例达到部分反应（残留增生过长的子宫内膜，无细胞不典型），2例、1例无反应或疾病进展；治疗全过程中分别有6例、20例共26例（87％，26／30）达到完全反应，中位完全反应时间6个月（3～21个月）。中位随访时间55．5个月（24～104个月），所有患者均存活。6例完全反应的子宫内膜癌患者中有3例复发，中位复发时间10个月（6～51个月）；20例达到完全反应的子宫内膜复杂性不典型增生患者中有7例复发，中位复发时间12个月（6～55个月），其中4例再次孕激素治疗后重新达到完全反应。26例完全反应患者中，8例进行了3～6个月的巩固治疗，有3例复发；18例未行巩固治疗，有7例复发；是否巩固治疗患者的复发率比较，差异无统计学意义（P=1．000）。子宫内膜癌患者治疗后正常妊娠4例次，21例子宫内膜复杂性不典型增生患者正常妊娠10例次，共成功分娩16例健康新生儿。（2）镜下观察：肿瘤性病变在用药后达到部分反应或完全反应者病变范围明显缩小甚至消失，腺体密度下降，腺体结构简单清晰，腺上皮层次变薄，异型性减轻或消失。子宫内膜对孕激素治疗的反应：表现为子宫内膜间质水肿及蜕膜化，腺体狭小、迂曲；腺上皮单层，核变小，胞质变丰富；达到部分反应或完全反应者随着用药时间的延长，腺上皮萎缩明显，间质蜕膜化，表现为抑制性分泌反应。伴随的化生性改变：孕激素治疗后易发生鳞化，多表现为不成熟性鳞化。结论Ⅰa期子宫内膜样腺癌及子宫内膜复杂性不典型增生病程进展缓慢，对孕激素治疗反应良好。治疗成功后复发率较高，大部分复发患者再次孕激素治疗安全、有效。保守治疗后需要长期随访观察。子宫内膜病理检查在保守治疗及长期随访中有重要作用。

Objective To assess the efficacy and pathological change of fertility-sparing treatment with progestin for endometrial carcinoma （EC） of stage Ⅰa and complex atypical hyperplasia （CAH） and to observe the prognosis of the treatment. Methods Nine EC patients of stage Ⅰa and 21 CAH patients aged under 40 years who desired childbearing and retaining their fertility were enrolled into this study. All patients were given a daily oral high-dose of progestin with duration of treatment ranging from 6 to 9 months. Diagnostic curettage was performed every 3 months as a modality for seeing the histologic change of neoplastic tissues and endometrial tissue. A careful and long-term follow-up is necessary for patients with complete response （CR）. Results During the first period of fertility-sparing management, according to histologic change, 5 EC patients and 18 CAH patients showed CR with no evidence of endometrial adenocarcinoma or hyperplasia, 2 EC patients and 2 CAH patients showed partial response with a regression to complex or simple hyperplasia without atypia, 2 EC patients and 1 CAH patient showed stable disease or progressive disease. Accordingly, a total of 26 patients showed CR （26 of 30 patients）. The median time to CR was 6 months （range, 3 to 21 months） of progestin treatment. The median follow-up time was 55.5 months （range, 24 to 104 months） and all patients were alive. During follow-up, among the 26 patients with CR, 3 of 6 EC patients achieved CR recurred disease after a median time interval of 10 months （range, 6 to 51 months）, 7 of 20 CAH patients achieved CR had recurrent disease after a median time interval of 12 months （range, 6 to 55 months）. Four of 7 CAH with recurrent disease achieved CR to progestin re- treatment. Eight of 26 patients achieved CR continued a further 3 or 6 months of consolidation therapy, 3 of them had recurrent disease, the remaining 18 stopped progesterone treatment after CR and 7 patients had recurrent disease; there was no significant statistical difference between the two groups （P=I.000）. EC patients succeeded in 4 pregnancies, CAH patients succeeded in 10 pregnancies, they gave birth to 16 healthy babies in all. Conclusions EC of stage Ⅰa and CAH had slow progression of symptoms. Progestin treatment in EC of stage Ⅰa and CAH patients was effective. A careful and long-term follow-up is required because of the substantial high rate of recurrence. Progestin re-treatment in most patients with recurrent endometrial cancer is effective and safe.