宫腔镜电切术联合孕激素对早期子宫内膜癌保留生育功能治疗8例分析

目的:探讨宫腔镜电切术联合孕激素对早期子宫内膜癌患者保留生育功能治疗的疗效和可行性.方法:回顾性分析本院2005年1月至2010年9月接受保留生育功能治疗的8例早期子宫内膜癌患者的临床资料.8例患者均给予宫腔镜下病灶及病灶下浅肌层电切,术后宫腔内放置左炔诺孕酮宫内节育器(LNG-IUD) 12个月.结果:在39个月的中位随访期间(11～77个月),1例术后5个月复发行子宫加双侧附件切除,随访期间未完全缓解;1例术后6个月子宫内膜增生,继续治疗后术后9个月完全缓解;其余6例均在术后3～6个月完全缓解.8例患者4例自然妊娠,其中1例流产,3例成功分娩.8例患者均无瘤存活.结论:在严格掌握适应证的前提下,对要求保留生育功能的早期子宫内膜癌患者行宫腔镜电切术联合孕激素治疗,在保留生育功能的同时其预后良好,是早期子宫内膜癌有益的治疗方案.     

宫腔镜手术联合孕激素治疗早期子宫内膜癌的临床分析

目的探讨早期子宫内膜癌患者宫腔镜手术结合孕激素保留生育功能治疗的临床有效性及可行性。方法回顾性分析西北妇女儿童医院2011年9月至2016年12月接受宫腔镜手术联合孕激素保留生育功能治疗的9例早期子宫内膜癌患者的临床及随访资料。结果 9例患者中,初次治疗完全缓解8例,复发1例,初次治疗结束后中位随访时间37个月(3~58个月),所有患者均存活。其中7例患者共妊娠8次,妊娠成功5例,4例患者足月或近足月活产儿。治疗期间5例患者出现体质量增加,2例出现乳房胀痛,1例肝功轻度异常,1例轻度宫腔粘连,经对症处理后均好转,无严重不良事件发生。结论在严格掌握适应证的前提下,对有强烈生育愿望的年轻早期子宫内膜癌患者行宫腔镜手术联合孕激素方案的保留生育功能治疗是安全、有效、可行的。     

年轻子宫内膜癌患者为保留生育功能孕激素治疗结局

为研究年轻子宫内膜癌患者内分泌治疗以保留生育功能的安全性,选取30(1970～2000)年间就诊的绝经前子宫内膜癌患者75例,其中年龄<40岁,需保留生育功能的13例首先进行孕激素治疗,其病理均经再次证实,进行随访。结果:13例平均年龄31(23～40)岁,6例在不孕症诊治中发现子宫内膜癌,其中4例有无排卵病史,另外7例因不规则阴道出血就诊发现子宫内膜癌。13例中11例诊刮标本为高分化腺癌,2例为中分化腺癌。全部患者接受孕激素治疗至少3个月,多数患者采用醋酸甲地孕酮160mg/d,其他还有醋酸甲羟孕酮(MPA)600mg/d、己酸孕酮2g/周或3g/周、炔诺酮5mg/d等…     

子宫内膜癌保留生育功能的治疗进展

子宫内膜癌是最常见的妇科恶性肿瘤之一,5%发生在40岁以下的妇女,年轻子宫内膜癌患者常强烈要求保留生育功能。生育年龄子宫内膜癌患者症状(月经异常)出现早,多为早期、分化程度好、且多数为性激素依赖型,预后较好。现已有早期子宫内膜癌采用保守手术及激素(通常为孕激素)治疗成功且保留生育功能、成功分娩的报道,现就子宫内膜癌保留生育功能治疗的现状做一综述。     

子宫内膜癌患者保留生育功能治疗的研究进展

子宫内膜癌好发于绝经前后的妇女,40岁以下者相对少见,只占所有病例的2.1%～14.4%.其治疗方法主要为子宫双附件切除,或同时行腹膜后淋巴结切除.此种手术治疗尽管对早期肿瘤的治愈率高,但患者却丧失了生育能力.一般情况下,年轻的子宫内膜癌患者多为有不孕史的未孕妇女,渴望保留生育功能.现已有早期子宫内膜癌采用反复子宫内膜诊刮及激素（通常为孕激素）治疗成功且保留生育功能的报道.保守性治疗尽管可行,但仍有许多问题存在争议,诸如恰当的治疗前评估,孕激素治疗的期限及剂量,完成生育后子宫切除的必要性等.因此,本文复习近年的国内外文献,就子宫内膜癌患者保留生育功能治疗的治疗前评估、治疗方法及结局的研究进展综述如下.     

年轻早期子宫内膜癌保留生育功能治疗

随着女性生育年龄的推迟,年轻早期子宫内膜癌患者比例将会逐步升高。考虑到多数年轻早期子宫内膜癌患者具有肿瘤分化程度好、病变局限和对孕激素治疗有效等特点,保留生育功能的治疗方式逐渐受到重视。文章就此问题进行简要阐述。     

大剂量孕激素治疗子宫内膜不典型增生及早期子宫内膜癌的疗效及妊娠结局分析

目的:探讨大剂量孕激素治疗子宫内膜不典型增生及早期子宫内膜癌的疗效及妊娠结局。方法:选择2014年1月至2018年12月广州医科大学附属第三医院就诊的年轻且有生育要求的子宫内膜不典型增生患者24例及早期子宫内膜样腺癌患者6例,分析应用大剂量孕激素保守治疗的临床效果及妊娠结局。结果:24例子宫内膜不典型增生患者中完全缓解20例(83.33%),部分缓解0例,疾病稳定1例(4.17%),疾病进展1例(4.17%),疾病复发2例(8.33%);20例完全缓解中1例未婚,余19例中成功妊娠10例(52.63%),其中4例足月分娩,3例孕中期双胎流产,2例孕早期流产,1例孕早期随访中;2例疾病复发患者继续药物治疗后均完全缓解,其中1例自然受孕后足月分娩。6例早期高分化子宫内膜样腺癌完全缓解3例(50.00%),部分缓解0例,疾病稳定2例(33.33%),疾病进展0例,疾病复发1例(16.67%);疾病稳定2例最终行子宫内膜癌全面分期手术,余4例保留生育功能患者目前未成功妊娠。结论:密切随访下,大剂量孕激素治疗子宫内膜不典型增生和早期子宫内膜癌是安全有效的。     

子宫内膜癌患者保留生育功能治疗

子宫内膜癌保留生育功能（简称“保育”）治疗，已经由规范化诊治进入到个体化治疗的时代。对于超出现有适应证的患者，需要探究其保育治疗的可行性和有效方案。影像、宫腔镜和病理，是评估病情和判断疗效的重要手段。治疗方案包括孕激素方案、非孕激素方案、联合用药方案等，需根据患者情况具体选择。助孕时机和策略尚需进一步探究。随访管理对于患者的长期预后具有重要意义。     

高分化子宫内膜样癌及子宫内膜重度不典型增生患者孕激素治疗的临床分析

目的探讨35岁以下高分化子宫内膜样癌及子宫内膜重度不典型增生患者采用孕激素治疗以保留患者子宫的疗效,并随访其治疗后的生育情况.方法采用回顾性分析的方法对1991年至2005年北京协和医院收治的35岁以下、接受孕激素治疗（以醋酸甲羟孕酮为主）的25例高分化子宫内膜样癌及子宫内膜重度不典型增生患者的临床病理资料进行研究.其中,子宫内膜样癌8例（内膜癌组）,子宫内膜重度不典型增生17例（不典型增生组）.孕激素治疗前对患者进行全面的分期评估,治疗后每1～6个月诊刮以评价疗效,对有生育要求者随访其生育情况.结果内膜癌组患者孕激素治疗前经全面的分期评估,证实为早期、高分化子宫内膜样癌.除1例子宫内膜样癌患者尚未评估疗效外,内膜癌组其他7例及不典型增生组17例患者治疗后有效者分别为6例（6/7）、17例（100%）;缓解者分别为5例（5/7）、14例（82%）;缓解后复发者分别为1例（1/5）、3例（21%）,复发时间为缓解后6～30个月;随访缓解后要求生育的14例患者中,内膜癌组4例患者尚未生育,不典型增生组10例患者中4例妊娠共7次.1例自然受孕后失访;3例经促排卵治疗后受孕并足月分娩,其中1例产后人工流产3次.结论对于要求保留子宫的高分化子宫内膜样癌及子宫内膜重度不典型增生的年轻患者,孕激素治疗是一种治疗选择.孕激素治疗前应对子宫内膜样癌患者进行详细全面的分期评估,辅助生殖措施的介入有望提高治疗后的妊娠率.     

早期高分化子宫内膜癌及子宫内膜不典型增生患者保留生育功能治疗的结局分析

目的:探讨早期高分化子宫内膜癌及子宫内膜不典型增生患者保留生育功能治疗的结局。方法:回顾性分析2010年1月至2017年12月就诊于北京大学第三医院要求保留生育功能的早期高分化子宫内膜癌患者43例及不典型增生患者77例的临床病理资料及治疗结局。结果:保守治疗的完全缓解(CR)率为96.67%(116/120),不典型增生组患者保守治疗3个月CR的比例显著高于子宫内膜癌组(74.03%vs 41.86%,P0.05)。109例患者有妊娠要求,妊娠率为43.12%(47/109)、活产率为33.03%(36/109)。分析显示,体质量指数(BMI)、是否癌变及合并有糖尿病或胰岛素抵抗与治疗缓解后能否成功妊娠有关(P0.05),而治疗获得CR的时间及缓解后维持治疗与妊娠无关(P0.05)。复发率为32.76%(38/116),中位复发间隔为17月,是否癌变(RR 5.624)是影响复发的独立危险因素(P0.05),达CR后的维持治疗(RR 0.385)及妊娠(RR 0.382)是影响复发的保护性因素(P0.05)。子宫内膜癌组的中位复发间隔为13月,子宫内膜不典型增生组为24月,两组差异有统计学意义(P0.05)。复发后重复孕激素治疗的有效率为100.00%(31/31)。结论:早期高分化子宫内膜癌和不典型增生的有生育要求的患者,保守治疗安全有效。保守治疗3个月子宫内膜不典型增生疗效好于子宫内膜癌。BMI、是否合并糖尿病和胰岛素抵抗及癌变与其妊娠有关,治疗达CR后的维持治疗并不影响妊娠,但治疗后复发率较高,妊娠和维持治疗是预防复发的保护因素。复发后重复保守治疗仍然有效。     

Reevaluating the safety of fertility-sparing hormonal therapy for early endometrial cancer

OBJECTIVE: To evaluate the safety of fertility-sparing hormonal therapy for endometrial cancer in young patients. METHODS: Six patients diagnosed with endometrial adenocarcinoma grade I and had undergone progestin treatment were reviewed. Four patients failed progestin treatment and were then found at surgery to have both endometrial and ovarian cancers. A clonality assay using the human androgen receptor gene as the X-linked polymorphic marker and immunohistochemistry for steroid hormone receptor expression were used to delineate the relation between the endometrial and ovarian lesions and to explore possible causes of treatment failure. RESULTS: The patients were followed for a mean of 48.8 months. Four of the six responded to the treatment at a mean of 3.5 months. Two of these patients had a recurrence within a mean of 4.5 months after their initial response. Two patients did not respond to progestin treatment. At surgery in those 4, both endometrial and ovarian tumors were found. All 6 are still alive, and 2 successfully delivered healthy infants. The clonality assay revealed an independent cell origin for the endometrial and ovarian lesions in 2 of the 4 women who failed progestin treatment. Progesterone receptors were absent in both endometrial and ovarian tumors in 2 of these 4 patients. CONCLUSION: The absence of progesterone receptors may relate to the failure of progestin treatment. The use of progestin treatment for well-differentiated early endometrial carcinoma should be cautious and requires very careful clinical evaluation before and after treatment.     

子宫内膜癌保留生育功能的治疗

未生育的年轻子宫内膜癌患者常常寻找保留生育功能的治疗方法。本文的主要目的是复习有关子宫内膜癌患者保留生育功能治疗的相关文献,探讨适合进行保留生育功能治疗的患者特征、治疗前的评估、治疗方案、疗效以及妊娠率。     

Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger

To clarify what constitutes the adequate management of uterine endometrial carcinoma in young women, we reviewed clinicopathologically 31 patients aged 40 years and younger between January 1991 and June 2004. As a primary treatment, 12 cases chose hormonal treatment with medroxyprogesterone acetate (MPA; 600 mg/day) due to no findings of myometrial invasion and diagnosis of a grade 1, well-differentiated adenocarcinoma. In remaining 19 cases, surgery was performed. All the 19 patients who received surgery as a primary treatment are alive, with no evidence of a recurrence of the disease. In the 12 patients who received hormonal treatment, 8 patients eventually received a hysterectomy because of recurrence or no response to MPA. Of these eight patients, myometrial invasion was recognized in three patients. One of the eight patients died of the metastasized disease to the liver and brain after hysterectomy. After hormonal treatment, 4 of the 12 patients were exempted from surgery and showed no evidence of recurrence. Two patients had viable children. Progesterone receptor was negative in one case that died. Careful consideration should be given to hormonal treatment with MPA for the conservative management of endometrial carcinoma in young women. Moreover, MPA is not always a consistent management for every patient.     

40岁以下子宫内膜腺癌患者的孕激素治疗--附六例报告及文献复习

目的 评价孕激素治疗40岁以下高分化、早期子宫内膜腺癌患者的有效性和安全性.方法回顾性分析复旦大学附属肿瘤医院1996年至2004年以孕激素治疗作为初次治疗的6例 40岁以下的高分化、早期子宫内膜腺癌患者的临床病理资料;同时检索近10年的国内外相关研究报道,发现相关病例56例,对以上两组资料进行综合分析.结果本组6例患者中,4例孕激素治疗有效,2例无效者行手术治疗.4例有效者中,2例分别于治疗后10个月和12个月出现复发而行手术治疗,故共有4例行子宫切除术,术后病理检查均未发现子宫外转移.6例患者随访至今均无瘤生存.文献报道的56例患者中,46例孕激素治疗有效,其中11例复发者中7例再次采用孕激素治疗,且5例再次获得完全缓解.此56例中,共有16例行手术治疗,15例无瘤生存,1例术后出现盆腔复发.本组6例患者治疗后无妊娠和分娩;文献报道的56例患者中,共有41次妊娠,并分娩40个婴儿,其中双胎4例,三胎2例.结论孕激素治疗40岁以下高分化、早期子宫内膜腺癌我们的经验尚少,虽难作评价,但国内外文献报道是安全可行的,并可达到妊娠和分娩的目的.     

Preserving fertility before assisted reproduction in women with endometrial carcinoma: case report and literature review

Fertility-preserving treatment with progestin may be considered in nulliparous women with well-differentiated endometrial carcinoma. Recently, assisted reproductive treatments have been performed to achieve a rapid pregnancy in such cases. This report evaluates a 39-year-old woman who admitted with menorrhagia and primary infertility. Owing to persistent menstrual irregularity and thick endometrium, a diagnostic office hysteroscopy with endometrial biopsy was performed and revealed a well-differentiated adenocarcinoma. Although the woman wished to retain her childbearing potential with conservative management followed by an assisted reproduction cycle, the repeated endometrial biopsies during progestin treatment revealed persistent adenocarcinoma. Complementary surgery was performed due to persistent endometrial malignancy, which noted well-differentiated endometrioid adenocarcinoma without myometrial invasion or extrauterine disease. A review of cases with endometrial carcinoma that have been treated with conservative management and a subsequent assisted cycle is also presented here. To date, there are 14 such reports, including 15 women and 21 healthy infants. However, obtaining remission and maintaining the reproductive capability may not always be possible, even in early-stage cases. Therefore, patient and physician should always consider carefully if fertility-preserving management is preferred after diagnosis of endometrial carcinoma.     

年轻早期高分化子宫内膜样腺癌患者保守治疗新进展

子宫内膜癌（EC）是常见的妇科恶性肿瘤,对年轻未生育的早期高分化子宫内膜样腺癌患者来说,保守治疗显得尤为重要。传统保守治疗药物包括孕激素、促性腺激素释放激素类似物（GnRHa）和芳香化酶抑制剂（AIs）等。宫腔镜电切术联合孕激素治疗是年轻子宫内膜样腺癌患者保留生育功能的新型治疗方式,在缓解率、妊娠率、不良反应发生率和复发率等方面优于传统保守治疗,但目前关于手术操作及术后激素治疗尚无统一标准。肥胖EC患者应治疗肥胖以降低复发风险,其中以减重手术效果最为显著、持久。现已证实减重手术对体质量指数（BMI）≥35 kg/m2的早期高分化子宫内膜样腺癌患者是有效干预。建议BMI≥35 kg/m2或BMI≥30 kg/m2且合并代谢综合征/2型糖尿病的年轻早期高分化子宫内膜癌患者,若经非手术治疗肥胖疗效不佳,可考虑以减重手术作为辅助治疗     

早期宫颈癌保留生育功能治疗后肿瘤和妊娠结局的多中心研究

目的探讨宫颈癌保留生育功能治疗后肿瘤和妊娠结局对临床的指导价值。方法选取北京市9个研究中心2008年1月至2012年5月55例保留生育功能治疗的宫颈癌患者为研究对象,收集临床资料及随访结果,对数据进行统计学分析。结果 55例中子宫颈鳞癌52例,子宫颈腺癌3例;FIGO（2009）分期ⅠA1期17例,ⅠA2期7例,ⅠB1期31例;48例行广泛宫颈切除＋腹膜后淋巴结切除术,7例行次广泛宫颈切除＋腹膜后淋巴结切除术;11例术前行新辅助化疗1～2疗程,9例术后进行1～6个疗程的化疗。术后完成随访53例（96.4%）,中位随访时间19.2个月,49例（92.5%）对目前生活质量满意。肿瘤结局和妊娠结局如下：①保留生育功能治疗后肿瘤复发1例（1.9%）;②治疗后有妊娠计划的26例患者中,9例（9/26,34.6%）共有11次妊娠;其中足月分娩6次（6/11,54.5%）,早产2次（2/11,18.2%）,自然流产（10周）、人工流产（8周）及药物流产（6周）各1次（1/11,9.1%）。结论广泛/次广泛宫颈切除术作为年轻早期宫颈癌患者保留生育功能的治疗方法,安全有效,妊娠结局良好。     

Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer

OBJECTIVE: To evaluate the safety of fertility-sparing hormonal therapy for endometrial cancer in young patients. METHODS: We reviewed the clinical and pathologic records of patients diagnosed with endometrial adenocarcinoma before the age of 40, who were treated and followed over a 30-year period in the Division of Gynecologic Oncology. All patients who underwent conservative management with progestins (n = 13) are the subjects of this study. RESULTS: Follow-up was available for all 13 patients, with a mean follow-up of 82 months. All patients responded to treatment within a mean period of 3.5 months, with normal pathology on follow-up endometrial samplings. Six patients had a recurrence within a period extending between 19 and 358 months (median 40 months). Four patients were treated with a second course of progestins, and all had a histologic complete response. As of the time of preparation of this report, nine healthy infants had been born, and all the patients remained without evidence of disease. CONCLUSION: Conservative management of well-differentiated endometrial carcinoma in young patients, combined with assisted reproductive technologies, if needed, does not seem to worsen the prognosis. This approach also provides the possibility of conceiving and carrying a normal pregnancy.     

Endometrial adenocarcinoma in women under 25 years of age

Ten cases of endometrial carcinoma in young women aged 15 to 25 years are presented. Seven of these ten patients exhibited the clinical characteristics of Stein-Leventhal syndrome; of these, three had evidence of polycystic ovaries. Nine of the tumors were well-differentiated, adenoacanthomas (six) or adenocarcinomas (three) and limited to the endometrium. In one case, a moderately differentiated adenosquamous carcinoma involved an ovary and the pelvic wall. Treatment consisted of curettage and progestogens in three patients, one of whom later bore two children. The remainder of the women were treated with abdominal hysterectomy and bilateral salpingo-oophorectomy and/or radiation therapy. All patients for whom follow-up data are available are alive and well without evidence of disease. It is concluded that in selected young patients with well-differentiated endometrial carcinoma limited to the endometrium, conservative hormonal therapy and curettage may be adequate treatment and may preserve fertility.