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.     

Persistence of endometrial activity after radiation therapy for cervical carcinoma

Radiation therapy is a proved treatment for cervical carcinoma; however, it destroys ovarian function and has been thought to ablate the endometrium. Estrogen replacement therapy is often prescribed for patients with cervical carcinoma after radiation therapy. A review of records of six teaching hospitals revealed 16 patients who had endometrial sampling for uterine bleeding after standard radiation therapy for cervical carcinoma. Fifteen patients underwent dilatation and curettage, and one patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy when a dilatation and curettage was unsuccessful. Six patients had fibrosis and inflammation of the endometrial cavity, seven had proliferative endometrium, one had cystic hyperplasia, one had atypical adenomatous hyperplasia, and one had adenocarcinoma. Although the number of patients who have an active endometrium after radiation therapy for cervical carcinoma is not known, this report demonstrates that proliferative endometrium may persist, and these patients may develop endometrial hyperplasia or adenocarcinoma. Studies have indicated that patients with normal endometrial glands have an increased risk of developing endometrial adenocarcinoma if they are treated with unopposed estrogen. Patients who have had radiation therapy for cervical carcinoma should be treated with estrogen and a progestational agent to avoid endometrial stimulation from unopposed estrogen therapy.     

Cytological diagnosis of endometrial cancer and preinvasive endometrial lesions. A comparison of the Endo-Pap sampler with fractional curettage

The value of the Endo-Pap endometrial cell sampling device in the cytological assessment of the endometrium was compared with fractional curettage. 318 symptomatic women were studied consecutively, among whom were 42 with malignant tumors of the uterus. Satisfactory material for cytological diagnosis of the endometrial state was obtained in 96%, whereas only 91% of the histopathological material was suitable for interpretation. 35 of 36 women with primary cancers of the corpus uteri had atypical endometrial cytology (sensitivity 0.97). Of 42 uterine cancers, including one metastatic ovarian carcinoma, two adenocarcinomas and three squamous carcinomas of the cervix, 40 were detected by endometrial cytology (sensitivity 0.95). All 5 cases of high grade cytological atypia in endometrial polyps or endometrial hyperplasia could be diagnosed by abnormal endometrial cytology and 4 of 5 patients with adenomatous endometrial hyperplasia were diagnosed correctly. Endometrial cytology obtained with the Endo-Pap sampler is a simple and cheap diagnostic method with which to detect endometrial cancer. It is also effective for diagnosis of preinvasive endometrial lesions with highgrade cytological atypia. Clinicians should recognize that out-patient investigation of the endometrial state by endometrial cell sampling with the Endo-Pap is reliable and can usually replace fractional curettage.     

Transvaginal sonography of the endometrium in postmenopausal women

The purposes of this study were to compare transvaginal sonographic scanning of the uterus and endometrium with histology obtained by endometrial biopsy or curettage and to determine whether the sonographic technique might be useful in the evaluation of postmenopausal women. Eighty postmenopausal women were studied. Of these, 65 were asymptomatic (38 on no hormone therapy and 27 on hormone replacement). Fifteen women underwent evaluation because of postmenopausal bleeding. In both groups, endometrial thickness of 4 mm or less as depicted by sonography correlated well with endometrial characteristics of decreased estrogen stimulation. However, in women with measured endometrial thickness between 5-8 mm, proliferative endometrium could not be distinguished from hyperplastic endometrium or, in one case, low-grade carcinoma. Large polyps and invasive carcinoma with myometrial extension were easily recognized.     

Cytologic evaluation of the endometrium in women with postmenopausal bleeding

The records of 143 patients who had postmenopausal bleeding and underwent diagnostic curettage were reviewed. Of these patients 69% had benign endometrial tissue and in 8% there was insufficient tissue for histologic interpretation; 23% of the patients had endometrial carcinoma. In order to ascertain if endometrial cytology could predict which patients which patients may be harboring endometrial carcinoma, a prospective study was carried out on 69 patients complaining of postmenopausal bleeding. Prior to curettage, an endometrial cell sample was obtained with a disposable endometrial cell sampler. The preliminary data indicate good correlation between endometrial cytology and histology. There was one false-negative cytology report and one false positive report. Such a technique could eliminate an endometrial curettage in those patients in whom there is no clinical suspicion of endometrial carcinoma and the cytology is negative.     

The role of vaginal scan in measurement of endometrial thickness in postmenopausal women

Transvaginal ultrasound scanning was performed on 111 postmenopausal women. Of these women, 103 had postmenopausal bleeding, and eight were undergoing hysterectomy. Of the 103 women with bleeding, 93 had dilatation and curettage (D&C) and 10 patients were treated conservatively with a repeat scan in six months. A correlation of ultrasound findings and endometrial histopathology was possible in 94 patients. In 59 of these (63%) the endometrium was atrophic and the ultrasound endometrial thickness was 5 mm or less. In 29 (31%) patients the endometrial histology was abnormal and ultrasound endometrial thickness was greater than 5 mm. In six patients the endometrium was atrophic, but the ultrasonic endometrial thickness was apparently greater than 5 mm due to intracavity fluid. We suggest that an endometrial thickness of 5 mm is an appropriate cut-off level for conservative management of patients with postmenopausal bleeding, or in screening for endometrial carcinoma.     

The role of vaginal scan in measurement of endometrial thickness in postmenopausal women

Summary. Transvaginal ultrasound scanning was performed on 111 postmenopausal women. Of these women, 103 had postmenopausal bleeding, and eight were undergoing hysterectomy. Of the 103 women with bleeding, 93 had dilatation and curettage (D&C) and 10 patients were treated conservatively with a repeat scan in six months. A correlation of ultrasound findings and endometrial histopathology was possible in 94 patients. In 59 of these (63%) the endometrium was atrophic and the ultrasound endometrial thickness was 5 mm or less. In 29 (31%) patients the endometrial histology was abnormal and ultrasound endometrial thickness was greater than 5 mm. In six patients the endometrium was atrophic, but the ultrasonic endometrial thickness was apparently greater than 5 mm due to intracavity fluid. We suggest that an endometrial thickness of 5 mm is an appropriate cut-off level for conservative management of patients with postmenopausal bleeding, or in screening for endometrial carcinoma.     

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.     

Value of endometrial aspiration cytology in assessing endometrial status

Cytologic findings of endometrial aspiration from 135 women was correlated with pathologic diagnosis of endometrium. The results indicate that different endometrial changes, such as hyperplasia, carcinoma and other malignant endometrial lesions, different phases of normal menstrual cycle and senile atrophy can be distinguished by endometrial cytology. The author suggests that aspiration cytology may serve as a supplement to the biopsy or curettage in the assessment of the status of the endometrium.     

Ovarian metastasis in women with clinical stage I endometrial carcinoma

BACKGROUND: The incidence of ovarian metastasis in women with clinical stage I endometrial carcinoma is generally reported to be 5%, leading to the practice of removing the ovaries at surgery even in young patients. METHODS: A retrospective study of 84 patients with clinical stage I endometrial cancer was carried out. Patients were excluded if the pathologic study revealed any evidence of extrauterine, apart from adnexal, spread or if the peritoneal cytology was positive. Patients with serous papillary or clear cell tumor histology were also excluded. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Only three (4%) patients were found to be in surgical stage IIIA, all three had grade 3 tumors. Of these patients, two had uterine serosal involvement and one had a microscopic tumor implant in a fallopian tube; none had ovarian metastasis. CONCLUSIONS: The risk of ovarian metastasis in women with well to moderately differentiated endometrial cancer, myometrial invasion limited to less than one half of the myometrium, negative peritoneal cytology and no evidence of metastatic lymph node spread is negligible. Young patients with a preoperative histological diagnosis of well to moderately differentiated endometrial carcinoma may be surgically staged, leaving the final decision regarding removal of the ovaries pending a thorough pathological review of the surgical specimens.     

Transvaginal endometrial sonography in postmenopausal women taking tamoxifen

OBJECTIVE: To evaluate sonographic measurements of endometrial thickness in postmenopausal women taking adjuvant tamoxifen therapy for breast cancer, and to correlate sonographic and pathologic findings to symptoms and duration of tamoxifen therapy. METHODS: Medical records and sonograms of 80 postmenopausal women treated for breast cancer with adjuvant tamoxifen therapy were reviewed retrospectively. Endometrial thickness was recorded as a single-layer thickness and considered abnormal when greater than 2.5 mm for postmenopausal women. Sonographic endometrial thickness was correlated to histologic findings, symptoms, and duration of tamoxifen therapy. RESULTS: Fifty-seven of 80 postmenopausal women (69%) had single-layer endometrial thicknesses of 2.5 mm or greater, measured by transvaginal sonography, and 55 of 57 had endometrial biopsies or dilatations and curettage. Biopsies detected 24 cases of abnormal endometria, including endometrial carcinoma (two), breast carcinoma metastatic to the endometrium (one), endometrial polyps (13), tubal metaplasia (three), and benign endometrial hyperplasia (five). Using a single-layer endometrial thickness greater than 2.5 mm by transvaginal ultrasound, 21 of 24 (87.5%) women with abnormal endometria were detected. Women with abnormal pathologic findings had a significantly thicker mean single-layer endometrial thickness than those with normal findings, 7 mm versus 4 mm (P < .01). Twelve women had postmenopausal bleeding, all of whom had a single-layer endometrial thickness greater than 2.5 mm on transvaginal sonography. CONCLUSION: With a sensitivity of detecting endometrial abnormalities of 84%, transvaginal sonography was useful for studying postmenopausal tamoxifen-treated women.     

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.     

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.     

Endometrial carcinoma in young women

Two hundred and fifty-four patients with endometrial carcinoma were diagnosed and treated from Feb. 1956 to Apr. 1987. Of these, 35 patients were below the age of 40 years at the time of diagnosis. These patients were analyzed and compared with those aged above 40. The main clinical manifestations were primary sterility and irregular menstruation. An endometrial carcinoma should be suspected in young women with menstruation disorder, sterility and follicular cyst of ovary refractory to treatment. The highly differentiated endometrial carcinoma in young women was easily confused with adenomatous hyperplasia and should be diagnosed with caution. In young patients with stage I well-differentiated disease desirous of childbirth, treatment by large dose of progestogens without hysterectomy may be the method of choice. Estimation of estrogen and progesterone receptors was very helpful in selecting therapeutic modalities and predicting prognosis. The difference of 5-year survival rates between these two groups of patients were not statistically significant.     

Adenocarcinoma of the endometrium in women 40 years of age or younger

Excluding cases associated with oral sequential contraceptives, adenocarcinoma of the endometrium in young women is rare, constituting about 3% of endometrial carcinomas. The present report, based on findings from one institution, notes that women 40 years of age or younger comprised 14.4% of the 111 patients with adenocarcinoma of the endometrium. Factors analyzed in patients 40 years of age or younger (group A) as compared with those 41 years of age or older (group B) include the following: obesity 43.8% (A) versus 17.9% (B), nulliparity 44% (A) versus 10.5% (B), hypertension 31.2% (A) versus 42.1% (B), and diabetes 6.2% (A) versus 21.1% (B). Patients in group A tended to have a well-differentiated tumor, and 31.2% had polycystic ovaries. Awareness of risk factors in young women who develop endometrial adenocarcinoma leads to earlier diagnosis and will preserve the historically excellent survival rate of young women.     

Diagnosis of endometrial carcinoma: predictive value of transvaginal color Doppler

The objective of this study was to determine whether transvaginal ultrasound plus color Doppler flow improve the ability to diagnose endometrial carcinoma and allow better discrimination between benign and malignant endometrial lesions. One hundred thirty women with abnormal uterine bleeding were evaluated with transvaginal color Doppler before fractional dilatation and curettage (D&C). The endometrial line thickness and endometrial characteristics were evaluated by endosonography. The resistive and pulsatile indices of the uterine arteries and of the endometrium were evaluated with transvaginal color Doppler. Following D&C and tissue diagnosis, women were divided into two groups, 62 with a histologic diagnosis of endometrial adenocarcinoma and 68 with benign endometrial tissue. All women with endometrial carcinoma underwent TAH and BSO. A complete histopathologic study was done an all surgical specimens. The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue grading were determined in all cases. The histopathologic findings were correlated with ultrasound and transvaginal color Doppler results. Patients with adenocarcinoma had an average endometrial thickness of 26.13 mm (range 8-87 mm). The average thickness for functional endometrium (proliferative) was 10.5 mm (range 6-23 mm). There was no case of carcinoma where the endometrial thickness was less than 8 mm. Intraendometrial neovascularization was not observed in any case with functional or atrophic endometrium. The flow indices in patients with endometrial adenocarcinomas are significantly different from the flow indices of patients with benign endometrial tissue. Transvaginal color Doppler increases the sensitivity of endometrial malignancy diagnosis. The method is capable of detecting important differences in flow indices and endometrial line characteristics between benign and malignant endometrial tissue.     

Atypical adenomatous hyperplasia of the endometrium

By women in climacterium and postmenopause the authors found 30 adenomatous atypical hyperplasias out of a total of 909 active hyperplasias. They also detected 68 endometrial carcinomas and 65 other changes. Out of 30 patients with adenomatous atypical hyperplasia, 23 had been subjected to curettage earlier but at that time had revealed only milder forms of hyperplasia. Surgery was performed in 21 patients: in 15 patients the diagnosis based on the operative preparation agreed with that based on curettage findings, in 2 patients endometrial carcinoma and in 2 patients glandular hyperplasia were detected, while in 2 patients there was no functional endometrium. Out of 9 patients who for various reasons were not surgically treated and represented an unintentional prospective study, 5 subsequently developed endometrial carcinoma, 3 mild forms of hyperplasia, and 1 atrophia cystica. In the authors' opinion, the histogenesis of endometrial carcinoma in late postmenopause is still an open question.     

Ultrastructural effects of estrogen replacement on postmenopausal endometrium

Endometrial adenocarcinoma occurs almost exclusively in postmenopausal women, and excessive or unopposed estrogen stimulation is suspect as a causative factor in its pathogenesis. Furthermore, the incidence of endometrial adenocarcinoma has increased in women undergoing estrogen replacement therapy. In the present study, the cellular response of premenopausal and postmenopausal endometrium to estrogenic stimulation was compared with endometrial adenocarcinoma by the electron microscope. Tissues were obtained at hysterectomy, endometrial biopsy, or endometrial curettage and were processed routinely for light and electron microscopy. Ultrastructurally the endometrium from postmenopausal patients undergoing estrogen replacement therapy was similar to normal cyclic endometrium in the late proliferative phase. At least three features of the estrogen-treated postmenopausal tissue resembled those observed in adenocarcinoma of the endometrium: accumulation of lipid droplets, irregular nuclei, and perinuclear whorls of microfibrils.     

Endometrial disease diagnosed by transvaginal ultrasound and dilatation and curettage.

BACKGROUND: This study is designed to compare endometrial thickness measured by transvaginal ultrasound with endometrial pathology by dilatation and curettage. METHODS: Fifty-four women with postmenopausal bleeding were evaluated. Endometrial thickness, including both layers of the endometrium, was measured by transvaginal ultrasound after which fractional curettage was performed and samples taken were then dispatched for histologic examination. RESULTS: Median endometrial thicknesses of 5 mm, 8.5 mm and 6 mm were found for benign, hyperplastic and carcinomatous endometrium, respectively. Of the eight hyperplastic samples, two cases had 4 mm, and one case had 3mm endometrial thickness. Similarly, of the nine malignant samples, three cases had an endometrial thickness of 3 mm. Three mm has been found to be the best cut off point for endometrial abnormalities in postmenopausal bleeding with 100% sensitivity but low specificity (13%). CONCLUSION: Fractional curettage seems to be the best method for detecting endometrial abnormalities in women with postmenopausal bleeding.     

Endometrial polyps and hyperplasia as risk factors for endometrial carcinoma. A case-control study of curettage specimens

As part of a comprehensive case-control study, the impact of previous endometrial pathology on the risk of developing endometrial carcinoma was investigated. The study comprised 254 consecutive women with histopathologically confirmed cancer of the uterine body in a well-defined population, and their age-matched controls. Ninety-eight (39%) of the patients and 81 (32%) of the controls had previously undergone endometrial curettage. More than one previous curettage was positively associated with endometrial carcinoma (odds ratio = 2.5; 95% CL = 1.4-4.5). Endometrial abnormalities in previous curettage specimens occurred significantly more often among carcinoma patients (57%) than among controls (25%) (odds ratio = 4.0; 95% CL = 2.0-8.0). Twelve patients, but no controls, had adenomatous hyperplasia and this hyperplasia antedated the cancer diagnosis by a mean of 4.6 years. Endometrial polyps were present significantly more often in patients (20%) than in controls (10%) (odds ratio = 3.4; 95% CL = 1.3-9.3). The present results suggest that both of these conditions are risk factors for endometrial carcinoma. Among women who had undergone endometrial curettage more than 4 years after the menopause, 19 out of 30 patients, but none out of 7 controls, showed abnormality in the curettage specimens. Postmenopausal women with endometrial abnormality should thus be regarded as being at risk of developing endometrial carcinoma.