Levonorgestrel-releasing intrauterine system (LNG-IUS) as a therapy for endometrial carcinoma

BACKGROUND: Primary treatment of endometrial cancer with progestogens is reserved for adjuvant or palliative treatment, although with unproven efficacy. CASE: We present a case of early endometrial cancer where a combination of oral progestogens and levonorgestrel releasing intrauterine system (Mirena) was used as a primary treatment, as the standard surgical treatment was deemed to carry an unacceptable mortality risk. CONCLUSION: Our treatment has resulted in reversion of the cancerous endometrial histological changes. This is encouraging, but obviously more cases and lengthier follow-up time are required in order to obtain more valid conclusions.     

Levonorgestrel intra-uterine system as a treatment option for complex endometrial hyperplasia

Objective

The objective of this study was to evaluate the potential treatment of atypical and non-atypical endometrial hyperplasia with the levonorgestrel intrauterine system (LNG-IUS).

Study design

A prospective observational study was undertaken at Queen's Medical Centre's menstrual disorder clinic between 2001 and 2008. Women presenting with abnormal perimenopausal and postmenopausal bleeding, underwent an endometrial biopsy followed by the insertion of a levonorgestrel intrauterine system (LNG-IUS). The study population comprised of 51 patients. The histology of 32 patients (Group A) showed complex hyperplasia without atypia, and in 19 patients (Group B), biopsy revealed atypical endometrial hyperplasia. These patients chose to be managed conservatively with repeat sampling of the endometrium.

Results

Group A: 28 (87.5%) patients out of 32 had regression of their endometrial hyperplasia within the first 12 months of follow-up. Three of the patients achieved regression by 24 months increasing regression rate to 96.8% and the remaining one had a hysterectomy due to a rare side effect. Group B: 16 (84.2%) of 19 patients had regression of the atypical hyperplasia after treatment with the intrauterine system within 12 months of treatment. One patient achieved regression of the hyperplasia by 24 months and two patients went on to have surgical management due to persistent atypia and severe atypia respectively.

Conclusion

This study contribute further evidence that illustrates that levonorgestrel intrauterine systems have a potential role in patients requiring non-operative management although close follow-up is essential.     

The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: An Australian study and systematic review

Background: The levonorgestrel intrauterine system (LNG-IUS) provides effective contraception and treatment for menorrhagia and is used to prevent endometrial hyperplasia (EH) in women taking unopposed oestrogens.
Aims: The aim of this study was to assess whether the LNG-IUS was also a safe and effective treatment for EH and to conduct a systematic review of the literature.
Methods: A retrospective record review was undertaken in a private gynaecology practice in Brisbane, Australia, and included all women with EH treated with hysterectomy, oral progestins or LNG-IUS between January 2004 and April 2007. Histopathological findings from hysterectomy specimens or endometrial biopsies were used to calculate rates of regression of the EH.
Results: Twenty-one women elected to have a hysterectomy and seven of those (33%) had no persisting hyperplasia at surgery. Twenty-six women had a LNG-IUS inserted at initial hysteroscopy dilatation and curettage or shortly afterwards; seven of those elected to proceed to hysterectomy when their diagnosis was known. Among ten women who used oral progestin treatment, 90% showed initial regression; two with recurrent EH were subsequently treated successfully with LNG-IUS. All 21 women (100%), including one with atypia, treated with LNG-IUS for more than seven weeks had normal endometrial histology on subsequent assessment. No women developed endometrial cancer. Pooled analysis of the published literature gave a 96% regression rate for non-atypical EH treated with LNG-IUS.
Conclusions: These data contribute further evidence that LNG-IUS is a safe and effective method for treating non-atypical EH. Whether LNG-IUS could provide a safe and cost-effective alternative to hysterectomy for atypical EH warrants further examination.     

Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of the atypical endometrial hyperplasia and endometrial cancer: retrospective data from selected obese menopausal symptomatic women

The aim of this retrospective study was to evaluate the efficacy of levonorgestrel intrauterine system-releasing (LNG-IUS) insertion in preventing atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in symptomatic postmenopausal overweight/obese women. A total of 34 overweight/obese postmenopausal women, presenting abnormal uterine bleeding (AUB) and endometrial hyperplasia (EH), and who were submitted to LNG-IUS insertion, were identified from registry data. Endometrial histology at LNG-IUS insertion showed simple EH in 20 cases (58.8%), complex EH in 14 cases (41.2%). At 36 months, 91% of patients showed no recurrence of AUB and a significant reduction in the mean endometrial thickness (from 8.2?±?2.2 to 3.2?±?1.5?mm, p < 0.05) was observed. Histologic regression of EH was observed in 27 (79.4%) and 33 (97.5%) cases at 12 and 36 months, respectively. None of the women in which EH persisted, reported cellular atypia or cancer progression at 12 and 36 months of follow-up. LNG-IUS represents an effective treatment option to manage postmenopausal obese women affected by AUB and EH. The device seems to be able to prevent the onset of AH and EC in women at high risk. Further prospective controlled studies in a well selected group of women are needed.     

Management of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection

Menorrhagia is the presenting symptom among the majority of women who undergo hysterectomy. The levonorgestrel intrauterine system (LNG-IUS) is highly effective in reducing menstrual bleeding. The aim of this randomized study was to compare the effect of endometrial resection (ER) as a surgical modality and the LNG-IUS as a hormonal modality for treating menorrhagia. This is a therapeutic, phase III randomized study that included 60 premenopausal women with excessive uterine bleeding. The patients were randomly allocated to two treatment groups – LNG-IUS or endometrial resection (ER). Uterine bleeding was quantified by the pictorial blood loss assessment score (PBAC). The degree of disturbance caused by menstrual bleeding on general well-being, work performance, physical activity and sexual activity was assessed using a visual analogue scale at screening. Initial evaluation was followed by reassessment at 6 months, and at 12 months or at discontinuation. Both groups were matched for age, duration of flow and uterine characteristics. In the LNG-IUS group, four patients discontinued treatment and, ultimately, treatment success was 77%. In the ER Group, all operations were uneventful. A significant reduction in the amount of blood loss monthly was achieved in 83% of the cases, and there was a significant improvement in the quality of life of the patients in both study groups. The difference between the two groups was not statistically significant (p=0.747). The placement of LNG-IUS has a dramatic effect in lowering bleeding intensity in menorrhagic patients, with the advantage of reversibility, and mild adverse events. It may be the first-line treatment in younger women with menorrhagia.     

Fertility sparing management of endometrial complex hyperplasia and endometrial carcinoma

The standard treatment of endometrial cancer or atypical hyperplasia is surgical removal of the uterus and ovaries. In early stage disease this has an excellent chance of cure but results in infertility. Although the majority of patients are postmenopausal an increasing number of patients with atypical hyperplasia or endometrial cancer are presenting with a desire to retain their fertile potential. In the last 8 years a number of studies have been published involving 403 patients with endometrial cancer and 151 patients with Atypical hyperplasia treated with high dose progestagens. The response rate is 76.2% and 85.6% respectively with endometrial cancer having a recurrence rate of 40.6%. There is a 26% recurrence rate in atypical hyperplasia. Overall 26.3% of those wishing to conceive had a live baby. Although concerns exist about the risks of medical treatment, those that fail this treatment do not appear to have a significantly poorer prognosis although 20 patients (3.6%) had either ovarian cancer or metastatic disease discovered during treatment or follow up.     

The utility of sentinel lymph node mapping in the management of endometrial atypical hyperplasia

Objectives

To determine the risk of endometrial cancer (EC) and lymph node involvement in patients with a preoperative diagnosis of “AH-only” versus “AH - cannot rule out carcinoma” and to study the value of SLN mapping.

子宫内膜癌及癌前病变危险因素的调查研究

目的:研究子宫内膜癌(EC)及癌前病变的流行病学特征及其发病的高危因素,为明确EC筛查的适宜人群提供依据.方法:选取2009年3月到2010年7月在北京大学第一医院妇产科行宫腔镜检查+分段诊刮术且同时行子宫内膜细胞学检查的540例患者.比较组织病理学诊断与子宫内膜细胞学筛查的结果.采用SPSS1O.0软件二分类非条件Logistic回归分析对影响组织病理学与子宫内膜细胞学结果的高危因素进行分析.结果:组织病理学结果为EC/非典型增生的相关危险因素:BMI≥25kg/m2、年龄≥40岁、糖尿病、高血压、绝经、恶性肿瘤家族史和毒物放射线接触史;独立危险因素:BMI≥25kg/m2、年龄≥40岁、糖尿病和恶性肿瘤家族史.子宫内膜细胞学报告为非典型腺细胞以上的相关危险因素:BMI≥23 kg/m2、年龄≥40岁、糖尿病、高血压、绝经和恶性肿瘤家族史;独立危险因素:BMI≥23 kg/m2和年龄≥40岁.结论:建议对年龄≥40岁或恶性肿瘤家族史的患者中进行EC的筛查;对肥胖、糖尿病的患者加强子宫内膜状况的监测.子宫内膜细胞学报告与病理学诊断的高危因素谱基本相同.     

Current management of endometrial hyperplasia-a survey of United Kingdom consultant gynaecologists

Objective

To determine current practice for the management of endometrial hyperplasia.

Study design

We carried out a web-based survey of all UK consultant gynaecologists, from the Royal College of Obstetricians and Gynaecologists (RCOG) database, to evaluate the current practice and to enquire whether a trial between oral progestogens and LNG-IUS for endometrial hyperplasia is required.

Results

We sent 1090 email invitations and 411 (37.7%) responded to this survey. In total, 338 consultant gynaecologists, who manage patients with endometrial hyperplasia, responded to all items of the survey. The oral progestogens (33.2%) and the LNG-IUS (52.1%) were the most popular choices for managing complex endometrial hyperplasia. The majority of the gynaecologists would explore two conservative choices before embarking into performing a hysterectomy for this condition (130, 52.6%). However, for atypical hyperplasia, the majority of the gynaecologists would perform a hysterectomy (273, 83.2%) and would only consider LNG-IUS or oral progestogens as a second or third option. Two hundred forty-four (72.2%) responded that an RCT for oral progestogens versus LNG-IUS for the management of endometrial hyperplasia is required. There were 171 (50.6%) gynaecologists that would be willing to randomise in such an RCT.

Conclusion

Our survey shows that complex endometrial hyperplasia is managed conservatively in UK, with oral progestogens or LNG-IUS, and atypical endometrial hyperplasia is managed with hysterectomy. An RCT, between oral progestogens and LNG-IUS for endometrial hyperplasia, is required to identify the optimum therapy.     

Is levonorgestrel intrauterine system effective for treatment of early endometrial cancer? Report of four cases and review of the literature

BACKGROUND: Intrauterine progesterone therapy potentially provides a simple alternative treatment for women with Stage I Grade I endometrial cancers who are at high risk for surgery. The case histories of four women with early endometrial cancer primarily treated with levonorgestrel intrauterine system (Mirena) are reported and the literature reviewed. CASES: Four women had Stage I grade 1 endometrial adenocarcinoma with positive progesterone receptor. All were assessed to be in American Society of anaesthesiologists risk class IV. After insertion of mirena intrauterine system, one woman (25%) had complete histological regression of disease within 6 months. One of three women who did not respond to treatment subsequently had a vaginal hysterectomy, which showed endometrial cancer with superficial myometrial invasion. CONCLUSION: This report raises doubts about the effectiveness of intrauterine progesterone therapy as a definitive alternative for the treatment of early endometrial cancer.     

Laparoscopic management of early endometrial cancer: current status

Endometrial cancer is the most common form of gynaecological cancer. Laparotomy has traditionally been the surgical treatment of choice, but the laparoscopic approach is gaining wider acceptance by gynaecologic surgeons, and an abundance of clinical information is currently available on all aspects of this approach. Whether in combination with laparoscopic-assisted vaginal or total laparoscopic hysterectomy, laparoscopic staging, including salpingo-oophorectomy and regional lymph-node dissection, is a major component of the treatment of patients with early endometrial cancer. This review examines the various options to treating endometrial cancer and proposes that laparoscopically assisted surgical staging of endometrial cancer is both a feasible and safe option. Comparative analyses of survival and recurrence rates for patients treated by laparoscopy and laparotomy have shown similar survival results. It remains to be proven if these laparoscopic techniques are associated with greater benefits.     

Endometrial hyperplasia involving endometrial polyps: report of a series and discussion of the significance in an endometrial biopsy specimen

Objectives  Endometrial polyps are a common cause of abnormal uterine bleeding. Rarely, a hyperplasia, either complex or atypical in type, is identified within a polyp in a biopsy or polypectomy specimen. Currently, it is not known whether the hyperplasia is likely to be confined to the polyp or also involve nonpolypoid endometrium. We aim to assess the likelihood of hyperplasia being confined to an endometrial polyp.
Design  In this study, we identified 32 women from pathology archives in whom endometrial hyperplasia was present within a polyp. The number of endometrial polyps during the study period was 1031 and therefore 3.1% of all endometrial polyps diagnosed during the study period contained a hyperplasia.
Setting  A major teaching hospital in the UK.
Methods  The biopsies were retrieved from the pathology archives of Royal Group of Hospitals, Belfast, between 2000 and 2006. We traced any follow-up biopsy or hysterectomy specimens to evaluate the status of the surrounding endometrium.
Results  The hyperplasias were complex ( n = 23) or atypical ( n = 9) in type. In 14 of 27 (52%) women in whom nonpolypoid endometrium was available for histological evaluation, either on the original biopsy or in a follow-up specimen, hyperplasia involved the nonpolypoid endometrium, and in three other women, hyperplasia was present in a polyp in follow-up specimens. Women with atypical hyperplasia in a polyp were slightly more likely to have hyperplasia in the surrounding endometrium than those with complex hyperplasia.
Conclusions  Our study illustrates that the risk of endometrial hyperplasia in a polyp concurrently involving nonpolypoid endometrium is significant. We suggest a strategy for the management of women with hyperplasia identified within an endometrial polyp in a biopsy or polypectomy specimen.     

Karyometry in atypical endometrial hyperplasia: a Gynecologic Oncology Group study

Objectives

Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC).

Methods

Cases from GOG study 167A were classified by a central pathology committee as AEH (n = 39) or SIEC (n = 39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis.

Results

Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is the percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve.

Conclusions

AEH comprises cases which may constitute a low risk group involving < 40% of AEH cases. These cases hold a percentage of < 20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have > 40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH esions might serve as criterion for assessment of risk for the development of invasive disease.     

Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature

Objectives

To investigate the efficacy of progestin treatment to achieve pathological complete response (pCR) in patients with complex atypical endometrial hyperplasia (CAH) or early endometrial adenocarcinoma (EC).

Methods

A systematic search identified 3245 potentially relevant citations. Studies containing less than ten eligible CAH or EC patients in either oral or intrauterine treatment arm were excluded. Only information from patients receiving six or more months of treatment and not receiving other treatments was included. Weighted proportions of patients achieving pCR were calculated using R software.

Results

Twelve studies met the selection criteria. Eleven studies reported treatment of patients with oral (219 patients, 117 with CAH, 102 with grade 1 Stage I EC) and one reported treatment of patients with intrauterine progestin (11 patients with grade 1 Stage IEC). Overall, 74% (95% confidence interval [CI] 65-81%) of patients with CAH and 72% (95% CI 62-80%) of patients with grade 1 Stage I EC achieved a pCR to oral progestin. Disease progression whilst on oral treatment was reported for 6/219 (2.7%), and relapse after initial complete response for 32/159 (20.1%) patients. The weighted mean pCR rate of patients with grade 1 Stage I EC treated with intrauterine progestin from one prospective pilot study and an unpublished retrospective case series from the Queensland Centre of Gynaecologic Oncology (QCGC) was 68% (95% CI 45-86%).

Conclusions

There is a lack of high quality evidence for the efficacy of progestin in CAH or EC. The available evidence however suggests that treatment with oral or intrauterine progestin is similarly effective. The risk of progression during treatment is small but longer follow-up is required. Evidence from prospective controlled clinical trials is warranted to establish how the efficacy of progestin for the treatment of CAH and EC can be improved further.     

子宫内膜增生并发子宫内膜癌的高危因素及预后分析

目的:研究子宫内膜增生患者并发子宫内膜癌的高危因素及其预后的分析。方法:回顾性分析2014年1月至2015年1月行全子宫切除术,且术前诊断性刮宫(诊刮)提示子宫内膜增生的74例患者的临床资料。根据全子宫切除术后的病理结果分为子宫内膜癌组(28例)和子宫内膜增生组(46例),对两组的临床特征进行比较,并分析发生子宫内膜癌的高危因素。结果:①74例患者中37.8%(28/74)并发子宫内膜癌。单因素和多因素分析结果均提示:年龄≥48岁和诊刮病理为重度子宫内膜不典型增生(重度AEH)为发生子宫内膜癌的高危因素(P0.05)。②不伴任何高危因素、伴有1个高危因素和2个高危因素的患者并发子宫内膜癌的几率分别为5.0%(1/20)、46.2%(12/26)和81.8%(9/11),差异有统计学意义(P0.05),且随着高危因素数目的增加发生子宫内膜癌的风险显著升高(OR 16.3,95%CI 1.9~140.3,P=0.011;OR 85.5,95%CI 6.8~1071.3,P=0.001)。③28例并发子宫内膜癌患者均为早期子宫内膜样癌,25例为高分化,3例为中分化。平均随诊13.3±6.3月,没有患者复发或死亡。结论:子宫内膜增生患者并发子宫内膜癌的发生率较高,特别是对于高龄(≥48岁)、诊刮病理为重度AEH的患者并发风险显著增加,但并发的子宫内膜癌多为分化较好的早期子宫内膜样癌,近期预后良好。     

Endometrial hyperplasia and the risk of carcinoma

Recent reports suggest that atypical endometrial hyperplasia diagnosed by biopsy or curettage is accompanied by a higher than expected risk of coexistent invasive cancer. In order to test this hypothesis we reviewed the pathology and clinical history of all patients at our institution who underwent hysterectomy for endometrial hyperplasia with or without cytologic atypia. We found 24 patients of 45 with a preoperative diagnosis of hyperplasia with cytologic atypia, and 21 with simple or complex hyperplasia without atypia. No cancers were found at surgery in the latter group nor were any significant historical differences found between the two groups. Of the patients with atypia, 12/24 (50%) had an endometrial carcinoma and nine patients (37.5%) were stage IB or greater. This is a significantly greater risk than previously reported in the literature. Endometrial hyperplasia with cytologic atypia may carry a higher risk of coexistent invasive endometrial carcinoma than previously believed. Methods to identify those patients at highest risk should be determined.     

子宫内膜非典型增生79例临床病理特征分析

目的 分析子宫内膜非典型增生患者的临床病理特征.方法 选择2007年3月至2010年7月北京大学人民医院收治的诊断为子宫内膜非典型增生患者79例,其中49例(62%)为单纯子宫内膜非典型增生(增生组),30例(38%)为子宫内膜非典型增生合并癌变(癌变组).回顾性分析子宫内膜非典型增生患者的临床病理特征[包括年龄、孕产次、体质指数(BMI)、绝经及阴道流血情况、合并症、B超检查等],并对两组患者进行比较.分析了分段诊刮及宫腔镜检查在子宫内膜非典型增生诊断中的价值.结果 (1)年龄:患者平均年龄为(50±11)岁,其中癌变组为(51±11)岁,增生组为(50±10)岁,两组比较,差异无统计学意义(P=0.994).(2)孕产次:两组患者孕产次分别比较,差异均无统计学意义(P＞0.05).(3)合并症:增生组和癌变组有合并症的患者分别为23例(47%)和13例(43%),两组比较,差异无统计学意义(P=0.755).(4)BMI:癌变组明显高于增生组[分别为(27.9±5.4)和(25.2±2.9)kg/m2,P=0.024].(5)绝经及阴道流血情况:绝经后患者癌变组为50%(15/30),增生组为31%(15/49),两组比较,差异无统计学意义(P=0.085);绝经后阴道流血患者癌变组为13/15,增生组为8/15,两组比较,差异无统计学意义(P=0.109);未绝经有月经改变患者癌变组为12/15,增生组为68%(23/34),两组比较,差异无统计学意义(P=0.590).(6)B超检查:癌变组阳性(指官腔有回声团)率明显高于增生组[分别为73%(22/30)和51%(25/49),P=0.050].(7)分段诊刮和官腔镜检查的诊断价值:行分段诊刮活检患者23例(29%)、宫腔镜活检44例(56%),两者对非典型增生的初次诊断率分别为87%(21/23)和93%(41/44),对非典型增生伴癌变的初次诊断率分别为6/12和12/16,诊断为非典型增生的患者中癌变的漏诊率分别为6/13和19%(4/21),分别比较,差异均无统计学意义(P＞0.05).结论 对于围绝经期异常阴道流血患者,应积极进行分段诊刮及官腔镜检查,分段诊刮或官腔镜活检诊断为子宫内膜非典型增生患者中,若其BMI较高或B超提示官腔有回声团,应警惕合并子宫内膜癌的可能.

Abstract：

Objective To explore the clinicopathological characteristics in atypical endometrial hyperplasia patients. Methods A retrospective study was carry out on 79 cases with atypical endometrial hyperplasia patients admitted to Department of Gynecology, Peking University People's Hospital from Mar.2007 to Jul. 2010. All patients were divided into two groups, hyperplasia group (merely atypical endometrial hyperplasia, 49 cases, 62%) and cancerization group (atypical endometrial hyperplasia accompanying endometrial carcinoma, 30 cases, 38%). Results The mean age of 79 cases were (50 ± 11) years old ,while they were (50 ± 10) and (51 ± 11) years old for hyperplasia group and cancerization group, there were not difference (P = 0.994). The gravidity and delivery frequencies were also not differently between two groups. The rates of complicated other diseases were 47% (23/49) and 43% (13/30), which was not significantly different (P = 0.755). The body mass index (BMI) of cancerization group was higher than that of hyperplasia group [(27.9 ± 5.4) vs. (25.2 ± 2.9) kg/m2, P = 0.024]. There were 50% (15/30) and 31% (15/49) menopause cases in two groups, respectively. Among them there were 13/15 and 8/15 cases showed vaginal bleeding. Among premenopausal patients, there were 12/15 and 68% (23/34) showed abnormal vaginal bleeding, but there were not significantly different between two groups (all P ＞ 0.05). The uterine cavity mass found by ultrasonography in the cancerization group patients was more than that in hyperplasia group [73% (22/30) vs. 51% (25/49), P = 0.050]. There were 23 cases (29%), 44 cases (56%) and 12 cases (15%) were diagnosed by dilatation and curettage (D&G), hysteroscopy and hysterectomy, respectively. The rates of diagnosing atypical endometrial hyperplasia by D&G and hysteroscopy were 87 % (21/23) and 93 % (41/44), respectively. The rate of diagnosis of canceration were 6/12 and 12/16, respectively. While, the rate of missed diagnosis of canceration in the atypical endometrial hyperplasia patients by D&G and hysteroscopy were 6/13 and 19% (4/21) ,respectively. Which all did not shown significantly different (P ＞ 0.05). Conclusion Hysteroseopy or D&G should be chosen on those peri-menopausal patients with abnormal bleeding, while those atypical endometrial hyperplasia patients with high BMI and uterine cavity mass diagnosed with D&G and ultrasonography should consider the possibility of canceration.     

子宫内膜增殖症保守治疗的疗效观察

目的:观察并评价不同保守治疗方案对子宫内膜复杂性增生(CH)及非典型增生(AH)的治疗效果、并发症及患者可接受性。方法:前瞻性研究2009年1月至2012年12月在山东大学齐鲁医院门诊及住院收治的50岁以下、病理结果证实为CH的患者116例,将患者随机分为3组,分别接受口服孕激素(A组)、口服避孕药(B组)或LNG-IUS(C组)治疗;AH的患者共90例,将其随机分为2组,分别接受口服孕激素或GnRH-a治疗。每3个月取子宫内膜行病理检查,随访观察患者治疗后的病理缓解率及不良反应。结果:(1)CH患者:治疗6个月时,口服孕激素治疗组、口服避孕药治疗组、LNGIUS组的病理缓解率分别为77.5%、73.7%和94.7%(P=0.039),治疗期间体重增加的发生率依次为42.5%、7.9%和2.6%(P=0.001),突破性出血发生率分别为15.0%、5.2%和26.3%(P=0.023),恶心呕吐症状发生率分别为7.5%、5.2%和2.6%(P=0.624)。(2)AH患者:治疗6个月时,口服孕激素治疗组、GnRH-a治疗组的病理缓解率分别为70.5%和60.9%(P=0.197)。口服孕激素治疗组患者出现的不良反应主要包括体重增加(59.1%)、突破性出血(22.7%)、恶心呕吐(13.6%)及头晕乏力(6.8%)。GnRH-a治疗组患者出现的不良反应主要包括潮热(67.4%)、阴道干燥(34.8%)、精神状态改变(32.6%)、头痛乏力(10.9%)。患者均未出现血栓形成及肝酶升高。结论:对50岁以下的CH患者,可首选宫腔内置入LNG-IUS系统。对AH患者,若无生育要求或手术禁忌证,应首选手术治疗;对于50岁以下选择保守治疗的患者,口服孕激素和GnRH-a治疗的疗效相当。保守治疗需在严格监测下进行,以便及时发现癌变。     

子宫内膜增殖症与子宫内膜癌细胞凋亡的相关性研究

目的：探讨子宫内膜增殖症和子宫内膜癌细胞凋亡及其与凋亡相关基因产物表达的关系。方法：应用ＴＵＮＥＬ法检测正常增殖期、增殖症及癌变子宫内膜组织标本的凋亡细胞,应用组免法检测Ｂｃｌ ２、Ｐ５３、Ｆａｓ及Ｆａｓ Ｌ抗原。结果：（１）与正常增殖期相比,增殖症子宫内膜腺上皮细胞中凋亡细胞比率高,Ｂｃｌ ２ 蛋白含量高,Ｆａｓ、Ｆａｓ Ｌ蛋白含量低下;（２）内膜癌癌细胞中凋亡细胞比率高,Ｂｃｌ ２蛋白含量低,１／３标本中Ｆａｓ、Ｆａｓ Ｌ蛋白含量丰富;（３）Ｐ５３ 仅存在于１２％ 的内膜癌细胞核内。结论：增殖症内膜凋亡细胞增多显示了良性病变内膜中细胞凋亡对过度增生的抑制。内膜癌细胞凋亡增多则与Ｂｃｌ ２ 低表达,Ｆａｓ、Ｆａｓ Ｌ高表达及Ｐ５３部分表达相伴,表明癌变内膜中细胞凋亡调控受多种基因表达的影响。