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/m~2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/m~2或BMI≥30 kg/m~2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。     

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.     

子宫内膜腺癌不孕症患者经药物治疗后行体外受精-胚胎移植术成功助孕1例

有研究报道持续性不排卵的不孕妇女发生子宫内膜癌的几率会增加10.3倍[1]。对于早期发现子宫内膜癌要求保留生育功能的年轻患者可考虑用大剂量孕激素药物保守治疗,病情缓解后可考虑立即妊娠。本文报道的是1例经过孕激素药物保守治疗缓解后的子宫内膜腺癌不孕患者     

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。     

早期子宫内膜癌患者保留生殖内分泌功能治疗的研究进展

子宫内膜癌（endometrial carcinoma,EC）为女性生殖道常见三大恶性肿瘤之一,近年来发病率有上升趋势。虽然子宫内膜癌大多发生于绝经后妇女,但也有约25%的患者为绝经前女性,且3%～14%发生在40岁以下。其中未生育的年轻患者很难接受失去生育机会及卵巢内分泌功能。因此,近年来子宫内膜癌保留生殖内分泌功能的治疗,即保留年轻EC患者的生育功能或卵巢内分泌功能成为较关注的问题。近年研究表明,以孕激素为主治疗希望保留生理功能的年轻、早期、高分化子宫内膜癌患者是相对安全有效的。综述子宫内膜癌保留生育及卵巢功能的治疗现状。     

早期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疗效及安全性分析

目的探讨早期子宫内膜癌(EC)及内膜不典型增生(AEH)保留生育功能治疗的疗效及安全性。方法回顾性分析2010年1月至2018年12月首都医科大学附属北京天坛医院收治的早期EC(20例)及AEH(25例)患者的临床资料,采用醋酸甲羟孕酮(MPA)或甲地孕酮(MA)口服,联合或单独使用左炔诺孕酮宫内缓释系统(LNG-IUD),随访6～60个月,分析治疗结局及治疗失败的原因。结果 EC组和AEH组的BMI、既往史、临床表现比较,差异均无统计学意义(P 0.05)。45例患者中,37例(82.2%)完全缓解,其中AEH组为92%,EC组为70%;3例(6.7%)部分缓解,均为EC患者在随访期间内经孕激素治疗后逆转为AEH;3例(6.7%)对治疗无反应,其中2例AEH患者经孕激素治疗3～6个月后仍为AEH,1例EC患者经孕激素治疗4个月后仍为EC;2例(4.4%)病情进展,其中1例EC患者为子宫内膜样腺癌G3ⅣB期,1例EC患者进展为子宫内膜样腺癌G1Ⅱ期。AEH组妊娠率为36.4%(6/11),EC组为22.2%(3/9)。1例肥胖患者(BMI42.68 kg/m~2)在服用MPA第4个月时发生了左侧横窦和乙状窦静脉血栓。结论早期EC及AEH保留生育功能的治疗是有效的,但仍存在病情进展及严重药物不良反应的风险。     

孕激素治疗子宫内膜非典型增生及早期内膜癌的研究进展

近年,子宫内膜癌（EC）的发生趋于年轻化,子宫内膜非典型增生（AEH）及早期EC的孕激素保守治疗得到了广泛的关注。现综述孕激素治疗AEH及早期EC的有效性,以及预测孕激素治疗有效性的可能生物标记,并探讨孕激素治疗抵抗的处理方法。     

早期子宫内膜癌保留生育功能治疗专家共识（2022年版）

<正>一、概述子宫内膜癌（endometrial cancer, EC）是女性生殖道常见恶性肿瘤,约25%的患者发生在绝经前,3%～5%的患者发病年龄<40岁,并且近年来年轻子宫内膜癌患者发病率呈上升趋势。约80%的年轻子宫内膜癌为Ⅰ型,分化良好。年轻子宫内膜癌患者的临床及病理特征为：(1)月经不规律,或不规则阴道流血,少数患者月经无异常;病史中经常合并肥胖、多囊卵巢综合征（polycystic ovarian syndrome, PCOS）及不孕不育等。(2)组织类型为子宫内膜样腺癌（endometrioid adenocarcinoma, EA）,     

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.     

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.     

Ovarian metastasis in a nulliparous woman with endometrial adenocarcinoma failing conservative hormonal treatment

BACKGROUND: There have been several reports about successful fertility-preserving treatment of endometrial carcinoma with subsequent pregnancy. However, conservative hormonal treatment for early-stage endometrial cancer still entails some risk. CASE: We present a 36-year-old nulliparous woman, initially diagnosed as clinical stage IA, grade 1 endometrial adenocarcinoma, receiving 6-month conservative treatment with remission achieved at 4 months from diagnosis. Recurrence at the endometrium was documented at the end of treatment. She underwent a definitive surgery including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. The final pathology revealed well-differentiated endometrioid adenocarcinoma with inner one-third myometrial invasion and right ovarian metastasis. CONCLUSION: This case report signals a warning that negative preoperative imaging studies are not reassuring for a relapsing low-grade, early-stage endometrial carcinoma failing conservative treatment.     

The role of MRI in the conservative management of endometrial cancer

BACKGROUND: Young patients with endometrial cancer who desire to preserve their fertility often decline hysterectomy in favor of conservative progestin therapy. Proper candidates should have disease confined to the uterus and a well-differentiated tumor. One of the evolving techniques to evaluate the extent of the disease and myometrial or cervical invasion is magnetic resonance imaging (MRI). CASE: A young patient with early-stage endometrial cancer initially declined surgery and was treated with megestrol. MRI suggested myoinvasion, and the patient consented to surgical staging. The final pathology revealed no residual carcinoma. CONCLUSIONS: The accuracy of MRI in detecting myoinvasion is limited, and as such results should be interpreted with caution when this information is used in counseling a young patient regarding surgical staging for endometrial cancer.     

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治疗的临床探讨

目的探讨早期子宫内膜癌患者保留生育功能治疗的适应证和治疗方法。方法对2003年11月至2007年9月佛山市第一人民医院接受保留生育功能治疗的6例早期子宫内膜癌患者,回顾性分析其临床资料、诊疗经过、近期疗效及妊娠结局。结果6例患者接受了以高效孕激素和反复宫腔镜检查与病灶去除为主的联合治疗,患者中位年龄31岁。子宫内膜样腺癌5例(高分化2例、中分化3例),中分化腺棘癌1例,6例雌、孕激素受体均阳性。1例治疗3个月获部分缓解,1例治疗不足3个月而未评估。其余4例均在治疗3～6个月内获完全缓解,其中2例患者分别于治疗结束后第2、4个月自然妊娠,新生儿均存活,其余2例暂未受孕。结论在严格掌握适应证的前提下对年轻且有强烈生育愿望的早期子宫内膜癌患者实施保留生育功能治疗是安全可行的,宫腔镜检查和定位活检可作为首选的评估和监测方法。肿瘤控制后应尽快妊娠,完成生育后应适时行手术治疗。     

Fertility-preserving treatment in young women with endometrial cancer

Nonsurgical fertility-preserving treatment of well-differentiated endometrial cancer with systemic progestins has been described for young women who desire to preserve their fertility. The overall response to progestin treatment in 9 retrospective studies is 79% with 79 subsequent live births. Recurrence can be expected in approximately 36-40% of conservatively treated patients who initially responded. Synchronous ovarian cancer has been reported in approximately 9%. However, amongst 162 receiving systemic, continuous treatment with progestins no death caused by cancer has been reported. We review guidelines for diagnosis, treatment and follow-up in young women undergoing conservative treatment for endometrial cancer.     

Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review

OBJECTIVE: We reviewed reported cases of grade 1 endometrial adenocarcinoma that were conservatively managed with hormonal therapy in an effort to identify the most effective treatment regimen. METHODS: We searched MEDLINE and other databases for English-language articles describing patients with grade 1 endometrial adenocarcinoma who were treated with hormonal therapy. The search included articles published between January 1966 and December 2003. The following key words were used: endometrial cancer, uterine cancer, adenocarcinoma, hormones, progesterone, medroxyprogesterone acetate, megestrol acetate, conservative therapy, fertility, and female. A total of 79 articles were found. Studies were excluded for the following reasons: advanced stage, metastatic or recurrent disease, progestin use after radiation, chemotherapy, or surgery, concurrent with radiation therapy or chemotherapy, administration of progestin other than orally or intramuscularly, tumor confined to a polyp, grade 2 or 3 disease, undocumented grade, nonendometrioid histology, progestin use in conjunction with ovarian wedge resection or other hormones, and hyperplasia. Our study ultimately included 81 patients in 27 articles. RESULTS: Sixty-two patients (76%) responded to treatment. The median time to response was 12 weeks (range, 4-60 weeks). Fifteen patients (24%) who initially responded to treatment recurred. The median time to recurrence was 19 months (range, 6-44 months). Ten (67%) of the patients with recurrence ultimately underwent total abdominal hysterectomy. Residual endometrial carcinoma was found in six patients (60%). Nineteen patients never responded. Twenty patients were able to become pregnant at least once after completing treatment. The median follow-up was 36 weeks (range, 0 weeks-30 years). No patients died of their disease. CONCLUSION: The majority of patients reported with well-differentiated endometrial adenocarcinoma who undergo conservative treatment with a progestational agent respond to treatment. When an initial response is not achieved or when disease recurs, carcinoma extending beyond the uterus is rare.     

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.     

Synchronous primary cancers of the endometrium and ovary in young women: A Korean Gynecologic Oncology Group Study

Objective

Some authors have recommended the use of diagnostic laparoscopy as a pretreatment assessment step for conservative hormonal treatment in young women with endometrial cancer. The aim of this study was to determine the incidence of synchronous primary cancer of the endometrium and ovary in young women.

Methods

The medical records of 3240 patients with endometrial cancer who underwent primary surgery between 1995 and 2010 were collected from 7 institutions and were retrospectively reviewed. Low-risk endometrial cancer was defined as tumors without myometrial invasion; normal or benign-looking ovaries; normal CA-125; grade 1 endometrioid histology; and early stage endometrial cancer on pretreatment assessment.

Results

Fifteen percent (471/3240) were younger than 40 years of age. The incidence of synchronous ovarian cancer in young women with endometrial cancer was 4.5% (21/471). In patients with low-risk endometrial cancer, synchronous cancers were not identified.

Conclusion

The incidence of synchronous ovarian malignancies in young women with endometrial cancer was quiet low (4.5%), unlike previous studies have revealed (11–29%). Therefore, diagnostic laparoscopy is not mandatory in patients with low-risk early stage endometrial cancer selected for conservative treatment to confirm the absence of ovarian malignancy.