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。     

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。     

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.     

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。     

子宫内膜不典型增生及早期子宫内膜样腺癌患者保留生育功能治疗的研究

目的探讨子宫内膜不典型增生及早期子宫内膜样腺癌患者保留生育功能的治疗方案、随访及生育指导。方法选取2016年9月至2018年5月中国医科大学附属盛京医院收治的24例子宫内膜不典型增生以及早期子宫内膜样腺癌患者,A组12例患者采用宫腔镜病灶切除术联合孕激素治疗,B组12例患者采用单纯孕激素治疗,所有患者密切随访至2019年2月。结果 A组完全缓解率为83%,B组完全缓解率为33%,差异有统计学意义(P=0.036),A组获得完全缓解时间为(6.33±2.23)个月,B组获得完全缓解时间为(6.75±2.03)个月;A组的部分缓解率为17%,B组的部分缓解率为33%,上述差异均无统计学意义(P0.05)。对影响获得完全缓解的相关因素进行分析,BMI≥30与不能获得完全缓解相关(P=0.01)。A、B两组妊娠率分别为25%和8%,两组患者的妊娠率比较差异无统计学意义(P0.05)。结论子宫内膜不典型增生及早期子宫内膜样腺癌患者保留生育功能治疗安全有效,宫腔镜病灶切除术联合孕激素治疗方案的完全缓解率高于单纯孕激素治疗方案。肥胖(BMI≥30)是影响患者完全缓解的危险因素之一,建议患者在治疗以及随访过程中应控制体重。     

宫腔镜下病灶电切术联合高效孕激素在保留生育功能子宫内膜癌患者中的临床价值

目的 探讨宫腔镜下病灶电切术联合高效孕激素治疗在保留生育功能子宫内膜癌（endometrial carcinoma, EC）患者中的临床应用价值。方法 回顾性分析郑州大学第一附属医院2012年12月至2020年12月行保留生育功能治疗的Ⅰa期EC患者的临床资料,共53例行宫腔镜手术,其中31例患者为宫腔镜下病灶电切术联合高效孕激素治疗作为电切组,22例患者为宫腔镜下诊刮术联合高效孕激素治疗作为诊刮组,每3个月行子宫内膜病理检查,分析两组患者的治疗效果及妊娠结局,并评估宫腔镜电切的临床价值。结果 （1）电切组与诊刮组的完全缓解率分别为87.1%(27/31)和72.7%(16/22),复发率分别为22.2%(6/27)、6/16,妊娠率分别为29.6%(8/27)、3/16,成功分娩率分别为5/8、2/3,宫腔粘连发生率分别为12.9%(4/31)、9.1%(2/22),均为轻中度粘连;两组患者的完全缓解率、复发率、妊娠率及宫腔粘连率比较,差异均无统计学意义（P>0.05）。logistic回归分析显示,宫腔粘连不是EC患者复发及妊娠的影响因素（P>0.05）。（2）电切组患...     

醋酸甲地孕酮和他莫昔芬治疗晚期子宫内膜癌的II期试验——GOG的一项研究

子宫内膜癌是最常见的妇科恶性肿瘤,晚期及复发的内膜癌患者预后较差,对细胞毒性药物化疗反应不佳且副作用较大。孕激素对子宫内膜癌有一定的治疗作用,但用药后会产生孕激素受体(PR)降调节,使得治疗反应时间较短。他莫昔芬(TAM)可以增加PR的表达,加强孕激素疗效。为了解醋酸甲地孕酮(MA)联合TAM对子宫内膜癌的治疗效果进行研究。美国妇科肿瘤学组(GOG)选取1994年7月～1995年11月间晚期/复发子宫内膜癌患者56例。给于MA80mg口服2次/d×3周,接着给予枸橼酸TAM20mg口服2次/d×3周,间隔3周后重复此治疗计划,直至肿瘤进展或出现严重副反…     

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。     

醋酸甲羟孕酮联合他莫昔芬治疗晚期子宫内膜癌的II期研究——GOG的一项研究

孕激素类药物对复发和转移的子宫内膜癌有效,但多数病例对孕激素反应时间较短,约4个月。他莫昔芬(TAM)可增加子宫内膜癌患者的孕激素受体含量,理论上,可以提高孕激素类药物对内膜癌的治疗效果,为证实这种假设进行本研究。选取1991年6月～1996年2月间有病理证实的复发或转移子宫内膜癌患者60例,给予TAM20mg口服,2次/d,每隔1周同时给予醋酸甲羟孕酮(MPA)100mg口服,2次/d,直至肿瘤进展或副反应阻止进一步治疗。结果:60例患者中病理类型主要有子宫内膜样腺癌32例(53.3%)、浆液性乳头状腺癌14例(23.3%)。高分化15例(25.0%),中分化17例(28.3%)…     

084醋酸甲地孕酮和他莫昔芬治疗晚期子宫内膜癌的Ⅱ期试验--GOG的一项研究

子宫内膜癌是最常见的妇科恶性肿瘤,晚期及复发的内膜癌患者预后较差,对细胞毒性药物化疗反应不佳且副作用较大.孕激素对子宫内膜癌有一定的治疗作用,但用药后会产生孕激素受体(PR)降调节,使得治疗反应时间较短.他莫昔芬(TAM)可以增加PR的表达,加强孕激素疗效.为了解醋酸甲地孕酮(MA)联合TAM对子宫内膜癌的治疗效果进行研究.     

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women

Purpose

To investigate the feasibility and efficacy of curettage with hysteroscopy followed by megestrol acetate (MA) for well-differentiated endometrioid carcinoma (EC) confined to the endometrium and for atypical hyperplasia (AH) in young women.

Patients and methods

Fourteen patients with EC and 12 patients with AH were prospectively enrolled in this study. All of the patients received at least 12 weeks of oral MA (160 mg/day) following thorough curettage with hysteroscopy. The response was assessed histologically every 12 weeks. The primary endpoint was the complete response rate. Adverse events, pregnancy rates and recurrence rates were secondary end points.

Results

Twenty-one (80.8 %) patients responded to treatment. The median time to response was 12 weeks. After a median follow-up of 32 months, 6 patients had recurrences. Significantly, more patients with infertility or PCOS experienced recurrence (P = 0.040, P = 0.015). Eight patients attempted to conceive after complete response; two spontaneous conceptions and one normal delivery were achieved. No disease-related or treatment-related deaths were observed.

Conclusions

Fertility-sparing treatment with MA following entirely hysteroscopic curettage is effective, demonstrating the least toxicity for rigorously selected young women with well-differentiated EC confined to the endometrium or with AH; however, close follow-up is required for the potential consequences of improper patient selection and a substantial rate of recurrence.     

Immunohistological localization of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate

Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. alpha 2-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for alpha 2-PEG before treatment although after MPA therapy all specimens obtained exhibited marked alpha 2-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize alpha 2-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of alpha 2-PEG production after stimulation with an oral progestogen.     

Endometrial carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate

BACKGROUND: Successful pregnancies after conservative progestin treatment to young women with endometrial carcinoma have recently been reported. However, it is not known for certain whether the lesion is completely eradicated in such patients. We present a case of residual endometrial carcinoma after term pregnancy which had been treated conservatively before the pregnancy began. CASE: A 28-year-old woman with endometrial carcinoma received conservative treatment with high-dose medroxyprogesterone acetate (MPA) and then conceived. After delivery at term, atypical cells were found in the endometrial curettage specimen. A hysterectomy was performed 6 months after delivery and revealed the presence of a small focus of intramucosal, grade 1, endometrioid-type adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had been effective, it had not completely eradicated the carcinomatous lesion, which remained during and after the term pregnancy.     

Two-year follow-up of patients with endometrial carcinoma after preoperative fluid hysteroscopy

Gücer F, Tamussino K, Reich O, Moser F, Arikan G, Winter R. Two-year follow-up of patients with endometrial carcinoma after pre-operative fluid hysteroscopy. Int J Gynecol Cancer 1998; 8 :476–480.
The aim of the present study was to analyze whether pretherapeutic hysteroscopy increases the recurrence rate in patients with endometrial cancer confined to the uterus. Between January 1993 and December 1995 a total of 33 patients with endometrial carcinoma underwent surgical staging following diagnostic fluid hysteroscopy and curettage at our department. Twenty-seven patients who had disease confined to the uterus without involvement of the uterine serosa formed the study group. Fifty-five patients with endometrial carcinoma confined to the uterus who had undergone surgery after diagnostic curettage without hysteroscopy during the same period were identified as controls. The median follow-up in the hysteroscopy group and the controls was 29 months (range 26–46) and 30 months (range 10–48), respectively. In the hysteroscopy group, no patient died of disease but one patient (3.7%) developed a local recurrence 37 months after primary treatment. In the control group, one patient (1.8%) had a local and para-aortic recurrence 20 months after primary treatment. Preceding diagnostic fluid hysteroscopy does not seem to increase the risk of early recurrence in patients with endometrial carcinoma histologically confined to the uterus.     

The fertility-sparing treatment in patients with endometrial atypical hyperplasia and early endometrial cancer: A debated therapeutic option

Fertility-sparing treatment may represent a realist option for accurately selected young patients with endometrial atypical hyperplasia or well differentiated, early endometrial cancer. Oral progestins, and especially medroxyprogesterone acetate (MPA) and megestrol acetate with different doses and schedules, represent the most commonly used hormone agents in this clinical setting. Approximately three fourths of the women achieve a histologically documented complete response, with an mean response time of 12 weeks, but about one third of these subsequently developed a recurrence after a mean time of 20 months. The expression of receptor for progesterone receptor (PR), PTEN gene, DNA mismatch repair gene MLH1 and phospho-AKT on tissue specimens may be useful for selecting patients fit for a conservative management. Several successful pregnancies have occurred after a fertility-sparing treatment of endometrial atypical hyperplasia or endometrial cancer, more frequently with assisted reproductive technologies. The implementation of in vitro fertilisation techniques not only increases the chance of conception, but it may also decrease the interval to conception. The opportunity of a demolitive surgery after delivery or after childbearing being no longer required is a still debated issue. Large multicenter trials are strongly warranted to better define the selection criteria for a conservative treatment, endocrine regimen of choice, the optimal dosing, the duration of treatment and follow-up protocols. In any case, the patient should be accurately informed about the relatively high recurrence rates after complete response to hormone treatment and expectations for pregnancy.     

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.     

Immunohistological localization of pregnancyassociated endometrial α2-globulin (α2-PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate

Summary. Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial α₂-globulin (α₂-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. α₂-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for α₂-PEG before treatment although after MPA therapy all specimens obtained exhibited marked α₂-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize α₂-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of α₂-PEG production after stimulation with an oral progestogen.     

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.     

Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study

OBJECTIVES: The objectives of this study were to estimate the clinical response rate and toxicity of daily tamoxifen combined with intermittent weekly medroxyprogesterone acetate (MPA). METHODS: This study reports the results of 61 patients with measurable advanced or recurrent endometrial carcinoma enrolled on this study to be treated with tamoxifen 40 mg p.o. daily plus alternating weekly cycles of MPA 200 mg p.o. daily. RESULTS: One patient was excluded and two patients did not receive study treatment. The percent of patients responding (6 complete and 13 partial) was 33% (95% confidence interval [CI]: 21-46%) among 58 eligible patients who received therapy. Median progression-free survival (PFS) was 3 months and median overall survival (OS) was 13 months. CONCLUSION: The combination of daily tamoxifen and intermittent weekly medroxyprogesterone acetate is an active treatment for advanced or recurrent endometrial carcinoma. Further investigation of this combination is appropriate.     

Fertility-preserving treatment of stage IA,well-differentiated endometrial carcinoma in young women with hysteroscopic resection and high-dose progesterone therapy

Objective

The standard treatment for endometrial cancer is surgery with hysterectomy. However, this procedure will cause infertility in young women who desire to preserve pregnant ability. Conservative management with hormone therapy has been shown to be satisfactory in both tumor control and fertility preservation. Recently, hysteroscopic tumor resection followed by progestin therapy has been reported to be an alternative strategy. In this study we present our experience with this approach.