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.     

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.     

宫腔镜联合孕激素治疗年轻患者早期子宫内膜癌的疗效及预后分析

目的:探讨宫腔镜联合孕激素治疗年轻早期子宫内膜癌患者的疗效及预后。方法:回顾性分析四川大学华西第二医院2008年1月至2014年12月自愿接受宫腔镜联合孕激素治疗的年轻早期子宫内膜癌16例患者的临床资料,且随访资料完整。所有患者行宫腔镜下刮宫或宫腔镜下病灶切除+刮宫,其中7例联合口服醋酸甲羟孕酮(250 mg/d,MPA组),9例联合醋酸甲地孕酮(160 mg/d,MA组)治疗。比较两组患者缓解、复发及生育等情况。结果:随访中位时间为54个月(17~90个月),其中12例(75.0%)完全缓解,3例(18.8%)部分缓解,1例(6.2%)无反应,MPA组和MA组的完全缓解率分别为71.4%(5/7)和77.8%(7/9),差异无统计学意义(P0.05)。16例患者中有3例在完全缓解后复发(MPA组1例,MA组2例),复发平均时间为42个月。16例患者中有8例(50.0%)完成了妊娠(其中1例2次妊娠),有6次(66.6%)妊娠顺利生产,3次(33.3%)流产。结论:宫腔镜联合孕激素治疗对于年轻早期子宫内膜癌患者保守治疗是有效的,其中MPA和MA的治疗效果无明显差异,但均存在着一定的复发风险,所以应对其进行严格的筛选和严密的随访。     

Endometrial carcinoma under the age of 40: reappraisal for oophorectomy in stage I disease

Objective: To reappraise the rationale of castration and the necessity of retroperitoneal lymph node biopsy in patients with endometrial carcinoma under the age of 40 years.Methods: A retrospective review of 30 patients under the age of 40 among 815 patients who had primary endometrial cancer treatment was carried out. The review consisted of clinical data, surgical pathology, and survival rates, as well as a comparative study of the literature.Results: The average age was 35.1 years. Three-quarters of the patients (76.6%) had stage I disease. Almost half of them had risk factors for endometrial carcinoma. The pathologic type was adenocarcinoma in 83% and grade 1 in 57%. Among 23 patients with stage I disease, 7 (30.4%) had no residual disease. Even with 16 patients found to have residual disease, 10 had it confined to the endometrium. Ovarian malignancy was only seen in 2 instances. Five demonstrated corpus luteum. Only 3 (13%) had lymph node metastasis and all in advanced disease. Six (20%) of these patients had delayed treatment more than 6 months. The follow-up was 5 months to 19 years. All are living and free of disease in stage I and stage II. Both patients with stage III disease died.Conclusions: In view of low risks in these young women with stage I disease, a thorough surgical staging including lymph node resection is desirable and hysterectomy with ovarian preservation is the treatment of choice. Oophorectomy might be considered in patients with cancer of the ovaries or in advanced stages of disease.     

Ovarian cysts in postmenopausal tamoxifen-treated breast cancer patients with endometrial thickening detected by transvaginal sonography

OBJECTIVE: To investigate the frequency of ovarian cysts in tamoxifen-treated postmenopausal breast cancer patients with endometrial thickening detected by transvaginal sonography. METHODS: Medical records and transvaginal sonographies of 38 postmenopausal women treated for breast cancer with adjuvant tamoxifen therapy who had undergone endometrial sampling due to abnormal endometrial thickness were reviewed retrospectively. RESULTS: During the study period five of 38 tamoxifen-treated postmenopausal patients (13.2%) had ovarian cysts. The mean tamoxifen treatment interval of the patients with an ovarian cyst was 22.4 +/- 18.4 months (p = 0.17). The mean endometrial thickness of the patients with an ovarian cyst was 12.6 +/- 5.9 mm (p = 0.17). Endometrial biopsy detected six cases of abnormal endometria, including endometrial carcinoma (n = 1), endometrial polyp (n = 1) and simple endometrial hyperplasia without atypia (n = 4). Three patients with ovarian cysts underwent laparatomy revealing simple cysts on histopathological examination. Two patients with ovarian cysts declined laparatomy and are currently under follow-up. CONCLUSION: Ovarian cysts a common side-effect of tamoxifen treatment in postmenopausal tamoxifen-treated breast cancer patients. Transvaginal sonography should be performed to detect any concomitant endometrial pathology.     

Is aortic lymphadenectomy necessary in the management of endometrial carcinoma?

OBJECTIVE: To evaluate the role of aortic lymphadenectomy in the management of endometrial carcinoma. METHODS: Clinical notes of 163 patients with endometrial carcinoma were reviewed. All patients had peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy with or without aortic lymphadenectomy. RESULTS: Seventy-five (46.0%) patients had pelvic lymphadenectomy alone whereas 88 (54.0%) had both pelvic and aortic lymphadenectomy. Thirty-five (21.5%) patients had nodal metastases with positive pelvic and aortic nodes in 26 (16.0%) and 24 (27.3%) patients, respectively. Isolated aortic metastases were found in 17 cases (19.3%). Among 35 patients with nodal metastases, recurrence developed in 15 (42.9%) patients and all except one died within five to 50 months. The remaining patients had a median disease-free period of 55 months (13-93 months). The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases, and all those who recurred died of disease within seven to 28 months. CONCLUSIONS: Our data suggest that aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high metastatic risk. After surgical removal and adjuvant radiotherapy, patients with nodal metastases achieved a better survival chance.     

Treatment of non-atypic endometrial hyperplasia using thermal balloon endometrial ablation therapy

BACKGROUND/AIM: Traditionally endometrial hyperplasias have been treated with progestins. Unfortunately, quite often hyperplasias are resistant to treatment, or they recur after therapy. The aim of the study was to compare traditional progestin administration with thermal balloon endometrial ablation in the treatment of non-atypic endometrial hyperplasia. METHODS: Women with endometrial hyperplasia (n = 34) were randomized in a 1:1 allocation ratio. Endometrial biopsy samples were taken 6 and 12 months after the treatment; if any signs of hyperplasia were detected, hysterectomy was performed. In addition, the hospital records were checked in September 2003 to observe for any later hysterectomy. Main outcome measures were recovery from hyperplasia and avoidance of hysterectomy. RESULTS: In patients treated with thermal ablation, the hyperplasias persisted at 6 or 12 months in 4 out of 17 patients, whereas the rate was 6 out of 17 patients in the progestin therapy group. According to patient records, 1 further patient treated with thermal ablation and 3 further patients treated with progestin were hysterectomized after the last visit. A total of 14 of the 34 patients (41%) have been hysterectomized so far. CONCLUSIONS: These preliminary results suggest that thermal balloon endometrial ablation therapy seems to be as effective as traditional progestin administration in the treatment of non-atypic endometrial hyperplasia. The hysterectomy rate during the follow-up period was, however, considerably high, and, therefore, hysterectomy might be considered even a first-choice treatment for endometrial hyperplasias.     

High-risk endometrial cancer in young indigent women

OBJECTIVE: The aim of this study was to evaluate a different prevalence and clinical pattern of high-risk endometrial cancer in an indigent population of young women. METHODS: Charts of 71 consecutive patients, treated for endometrial adenocarcinoma during a 6-year period, were reviewed. The patients were divided into two groups contingent upon age--(i) those who were below 40 years and (ii) those who were over 40. Based on histological type, grade, and stage, both groups were subdivided into a low, intermediate, or high-risk cancer category. RESULTS: Of the 13 (18.3%) patients in the younger age group, five patients (38.4%) had high-risk endometrial cancer, compared to only eight patients (13.8%) in the older age group. CONCLUSION: In contradiction to previous reports, our results show that a higher proportion of young indigent women diagnosed with endometrial cancer have a high-risk cancer. Delay in diagnosis can explain only some of the discrepancies in the special clinical pattern of endometrial cancer among this population. Other possible explanations include nutritional differences, genetic susceptibility, immunological status, and high-risk behavior. More epidemiological studies are needed for complete understanding of the unfavorable outcome of endometrial cancer in these young women.     

Treatment of advanced or recurrent adenocarcinoma of the endometrium with doxorubicin and cyclophosphamide

Thirteen patients with recurrent or advanced endometrial carcinoma were treated with a combination of doxorubicin (40 mg/m2 IV) and cyclophosphamide (600 mg/m2 IV). All patients had been refractory to prior radiotherapy and hormone therapy. None of the patients had received prior chemotherapy. Six of the 13 patients (46%) achieved an objective response: 1 complete response (8%) and 5 partial responses (38%). Median overall survival was 10 months (range 3-20 months). Doxorubicin and cyclophosphamide is an active combination in patients with advanced endometrial cancer.     

Coexisting ovarian malignancy in young women with endometrial cancer

OBJECTIVE: In premenopausal women with endometrial cancer, ovarian preservation may be a consideration. Our objective was to examine the occurrence of coexisting ovarian malignancy and to identify predictors of adnexal involvement. METHODS: With institutional review board approval, a retrospective chart review was conducted of young women with endometrial cancer identified at 4 affiliated institutions from 1996 to 2004. RESULTS: Among 102 young women (aged 24-45 years) who underwent hysterectomy for endometrial cancer, 26 (25%) were found to have coexisting epithelial ovarian tumors: 23 were classified as synchronous primaries, and 3 as metastases. Ovarian cancer histology was endometrioid in 92% of cases. Among the 26 cases of coexisting ovarian involvement, 12 (46%) had grade 1 endometrial cancer on preoperative biopsy, 4 (15%) had normal preoperative imaging of the adnexa, and 4 (15%) had benign-appearing ovaries at the time of intraoperative assessment. On final pathology, 18 of 26 cases (69%) occurred in patients with grade 1 endometrial cancers, and 15 (58%) occurred with inner myometrial invasion. Our study further highlights the risk of conservative management with 1 case of ovarian cancer diagnosed 9 months after hysterectomy with ovarian conservation for a stage IA, grade 1 endometrial cancer and a case of advanced endometrial cancer metastatic to the ovaries developing 3 years after successful resolution of a grade 1 endometrial cancer treated with megestrol acetate (Megace). CONCLUSION: Careful preoperative and intraoperative assessment of the adnexa is mandatory in young women with endometrial cancer. Those who desire ovarian preservation should be counseled regarding the high rate of coexisting ovarian malignancy.     

Reporting Normal Endometrial Cells in Pap Smears: An Outcome Appraisal

OBJECTIVE: The purpose of this study was to determine the clinical relevance of reporting the presence of normal endometrial cells in the Pap smears of women over the age of 35 years and the significance of this practice as it relates to patient management. METHODS: From January 1992 to December 1995, normal endometrial cells were reported in 206 consecutive Pap smears of women over the age of 35 years. Clinical follow-up was available for all patients, including the results of diagnostic procedures whenever performed. RESULTS: Of the 206 women with normal endometrial cells in their Pap smears, 162 presented with the chief complaint of abnormal vaginal bleeding. They were all evaluated by direct endometrial sampling, resulting in detection of 10 endometrial hyperplasias and 7 endometrial carcinomas. The remaining 44 women who were clinically asymptomatic were followed up with only routine annual gynecologic examinations for a minimum of 3 years. All had negative clinical courses. CONCLUSION: Reporting the presence of normal endometrial cells in Pap smears has little, if any, impact on subsequent patient management. Women who present with abnormal uterine bleeding are worked up for endometrial disease regardless of their Pap smear findings. In clinically asymptomatic patients, practitioners may, and in our experience often do, choose to disregard normal endometrial cells in Pap smear reports. The negative follow-up for the asymptomatic women in our study supports this practice. Therefore, reporting the presence of normal endometrial cells in Pap smears is of no clinical relevance and may, in fact, create a management dilemma for clinicians.     

Prediction of endometrial ablation success according to perioperative findings

OBJECTIVE: The aim of this study was to determine which factors in the perioperative period influence the success of endometrial ablation in alleviating menorrhagia. STUDY DESIGN: We performed a retrospective chart review of 120 women aged 27 to 49 years who underwent endometrial ablation after 2 months of preoperative treatment with danazol (Danocrine, 800 mg/d orally) or leuprolide (Lupron, 3.75 mg in one intramuscular injection each month). Patients who required medical management or additional operations to control the vaginal bleeding during follow-up (median follow-up, 37 weeks) were considered to have ablation failures. RESULTS: Sixty-three percent of patients (76/120) had a successful procedure. The chance of success was greater if a cavity of normal appearance was found (odds ratio, 2.3; P =.04). The finding of an intramural fibroid before the procedure resulted in a reduced trend toward success (odds ratio, 0.4; P =.06). The use of danazol pretreatment improved the rate of success overall (odds ratio, 2.2; P =.05) and especially among women <40 years old (P =.01) CONCLUSION: Perioperative findings may provide useful information in counseling patients regarding endometrial ablation. Success is greater among patients with a normal intrauterine cavity and after preoperative treatment with danazol.     

Fertility-Sparing Management Using Progestin for Young Women with Endometrial Cancer From a Population-Based Study

Objective

For young women with complex atypical endometrial hyperplasia (CAH) and endometrial cancer (EC) who choose to preserve fertility, progestin therapy is the mainstay of treatment. The objective of this study was to evaluate oncologic and reproductive outcomes associated with progestin therapy among these women from a population-based cancer registry.

The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers – a study of the National Cancer Institute of Canada Clinical Trials Group

A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.     

Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia

OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.     

Three-year follow-up results of polypectomy with endometrial ablation in the management of endometrial polyps associated with tamoxifen in Chinese women

Objective

The aim of this study was to investigate the role of hysteroscopic polypectomy with endometrial ablation in the management of tamoxifen-associated endometrial polyps in postmenopausal women with a more than 3-year follow-up period.

Study design

The medical records of 76 postmenopausal patients on tamoxifen who were performed hysteroscopic polypectomy with endometrial ablation were evaluated more than 3 years after the procedure with recurrence of polyps, recurrent abnormal uterine bleeding and surgical re-intervention.

Results

Average follow-up period was 74.91 ± 20.84 months. No patient underwent hysterectomy, 7 of 76 patients had a surgical re-intervention representing a total of 90.8% avoidance of additional surgery during the follow-up period, and 4 patients had a recurrent endometrial polyp representing the recurrence rate was 5.3%. 3 of 41 patients with postmenopausal bleeding had a recurrent abnormal uterine bleeding representing symptomatic relief rate is 92.7%. The treatment failed in 7 patients who requested surgical re-intervention: 4 patients requested a repeat polypectomy and ablation, 1 patient requested a repeat ablation and 2 patients requested a repeat hysteroscopy with uterine adhesion. No malignant endometrial pathological result was found.

Conclusions

For postmenopausal patients suffering from endometrial polyps associated with tamoxifen, hysteroscopic polypectomy with endometrial ablation continues to be proven as a safe and effective minimally invasive treatment method. The high rate of surgical re-intervention avoidance, great symptomatic relief and low recurrence rate are very encouraging for this technology.     

Fertility and tumor recurrence rate after conservative laparoscopic management of young women with early-stage borderline ovarian tumors.

OBJECTIVE: To evaluate the efficacy of laparoscopic conservative surgery in young women with borderline ovarian tumors who want to preserve their childbearing potential, and to assess whether pregnancy influences the recurrence rate during the follow-up evaluation period. DESIGN: Retrospective study. SETTING: Center for Reconstructive Pelvic Endosurgery, Reproductive Medicine Unit, S. Orsola Hospital, University of Bologna, Italy. PATIENT(S): Nineteen women (mean age 27.4 +/- 4.7) with borderline ovarian tumors who underwent laparoscopy between January 1995 and January 1998. All of the women wanted to preserve their fertility. INTERVENTION(S): A standardized conservative laparoscopic approach and a strict follow-up schedule. MAIN OUTCOME MEASURE(S): A complete preoperative examination. RESULT(S): Follow-up evaluations (mean 42 +/- 19 months) were made available to all patients. Among 19 patients, 10 attempted pregnancy and 6 conceived spontaneously. All six pregnancies went to term and the disease did not affect the gestation or the follow-up period after the pregnancy (24.5 +/- 15.7 months). CONCLUSION(S): Conservative laparoscopic management of borderline ovarian tumors is a potentially safe alternative in young women who want to retain their childbearing potential. Fertility and pregnancy outcome remain excellent in these women. Our preliminary data seem to indicate that the recurrence rate after pregnancy is not influenced by this approach.     

Allogeneic stem cell transplantation for patients with high-risk myelodysplastic syndrome.

Allogeneic stem cell transplantation (allo-SCT) is the only treatment with curative potential for patients with myelodysplastic syndrome (MDS). From June 1986 to April 1997, we treated 12 patients with primary MDS (5 men, 7 women, median age, 36.5 years) by allo-SCT. All patients had one or more of the following poor prognostic factors: intermediate-2 or high-risk categories according to the International Prognostic Scoring System; disease progression during follow-up; heavy transfusion requirements and recurrent infections. The median duration from diagnosis of MDS to allo-SCT was 6 months. The preconditioning regimen included total body irradiation combined with either high-dose cytarabine (n = 6), high-dose cyclophosphamide (n = 4), or other regimens (n = 2). Ten patients received bone marrow transplantations and two patients received peripheral blood stem cell transplantations. Prophylaxis for graft-versus-host disease (GVHD) consisted of standard cyclosporin and short-course methotrexate. Acute GVHD of grade 2 or above occurred in 10 patients, while chronic GVHD occurred in seven of the nine patients who survived longer than 6 months after allo-SCT. With a median follow-up of 50 months, all nine patients with human leukocyte antigen (HLA)-matched sibling donors survived. One patient had a relapse 6 months after transplantation and achieved complete remission again with low-dose cytarabine therapy. The three patients receiving allo-SCT from unrelated or HLA-mismatched donors died of grade 3 to 4 acute GVHD and infection within 5 months after transplantation. The estimated disease-free survival at 4 years was 67% (95% confidence interval, 40-93%), and the overall survival was 75% (95% confidence interval, 50-99%). Our data suggest that allo-SCT should be considered early in the clinical course for young MDS patients with a poor prognosis and a matched sibling donor.