绝经后子宫内膜息肉合并子宫内膜不典型增生及子宫内膜癌高危因素分析

目的分析绝经后妇女子宫内膜息肉(endometrial polyps,EMPs)发生恶变的相关危险因素。方法回顾性分析2001年4月至2009年12月北京大学人民医院妇产科收治的489例经宫腔镜病理确诊为EMPs的患者,依据病理类型分为良性组(471例)和非典型增生/恶性组(18例),比较两组患者的临床特征和子宫内膜息肉恶变的相关危险因素。结果绝经后子宫内膜息肉患者中,子宫内膜息肉合并不典型增生者11例(2.20%,11/489),子宫内膜息肉合并子宫内膜癌者7例(1.43%,7/489)。单因素分析的各临床因素中,绝经≥10年(OR=15.60,95%CI:2.05～118.57)和绝经后出血(OR=4.08,95%CI:1.31～12.70)是与子宫内膜癌前病变或子宫内膜癌相关的危险因素(P<0.05),而高血压、糖尿病、肥胖和子宫内膜息肉病史等因素比较,差异无统计学意义(P>0.05)。结论绝经后子宫内膜息肉发生癌前病变和子宫内膜癌风险增加,绝经≥10年和有绝经后出血症状是发生癌前病变和癌的危险因素。     

子宫内膜癌流行病学及发病因素

子宫内膜癌是女性生殖道三大恶性肿瘤之一,在欧美国家其发病率已占妇科恶性肿瘤的第一位。近年来,包括我国在内的许多发展中国家经济高速发展,人们生活习惯及饮食结构西方化,肥胖人群增多,以及非正规的激素替代治疗等多种因素导致内膜癌发生率明显上升,成为严重威胁发展中国家女性健康的生殖道恶性肿瘤。内膜癌的高危因素包括单纯雌激素的长期刺激、肥胖、糖尿病、高血压、不孕和绝经延迟等。     

Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer

AIM: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed. METHODS: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent. RESULTS: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P < 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%). CONCLUSION: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.     

Analysis of risk factors for recurrence and effective adjuvant therapy in patients with endometrial cancer

Objective: The aim of this study was to explore risk factors for recurrence and effective adjuvant therapy in endometrial cancer.

Methods:

Methods: Between 1985 and 1999, 170 patients with uterine endometrial cancer received initial therapy at the National Defense Medical College Hospital. We retrospectively analyzed risk factors including; histopathological features, operative procedures, adjuvant therapies and surgical staging.

Results:

Results: Although the prognosis in stage I and II patients was fairly good, recurrences were observed in patients with stage Ib or worse. Vagina walls were the frequent site of recurrence. About a half of relapses which occurred within seven months after surgery were observed during adjuvant chemotherapy. Multivariate analysis revealed that myometrial invasion ( P = 0.0231) was the only risk factor for recurrence. Although the prognosis in stage III and IV patients was generally poor, serosal invasion in stage III disease seemed to be an im-portant risk factor. With regard to adjuvant therapy in stage I–III patients who could receive optimal cytoreductive surgery; the risk of recurrence was significantly ( P = 0.0127) lower in patients receiving radiation therapy than in those receiving chemotherapy including platinum agents.

Conclusion:

Conclusion: The data suggested that in stage I–III patients with optimal cytoreductive surgery, myometrial invasion is an independent risk factor for recurrence and radiation therapy is more effective than chemotherapy as adjuvant therapy.     

Positive peritoneal cytology in endometrial cancer: enhancement of other prognostic indicators

OBJECTIVE: The goal of this study was to investigate the prognostic significance of positive peritoneal cytology in endometrial cancer. METHODS: A clinicocytopathological study was performed in 534 patients with endometrial cancer to assess the prognostic value of positive peritoneal cytology. The study population was divided into three groups: a low-risk group (disease limited to the uterus, grade 1, and depth of invasion < or =1/2), a moderate-risk group (disease limited to the uterus, grade 2 or 3, and/or depth of invasion >1/2), and a high-risk group (extrauterine disease). In each group, disease-free survival was compared in the patients who were positive or negative for malignant cells. RESULTS: The overall incidence of positive peritoneal cytology was 22.3% (119/534). The 5-year disease-free survival of patients positive or negative for malignant cells was 98.1% versus 100% in the low-risk group (n = 250), 77.5% versus 91.3% in the moderate-risk group (n = 211), and 42.9% versus 72.1% in the high-risk group (n = 73). A significant difference was noted in the moderate-risk (P = 0.044) and high-risk (P = 0.015) groups, but not in the low-risk group (P = 0.56). CONCLUSIONS: Positive peritoneal cytology is not a negative prognostic indicator itself, but it potentiates other prognostic indicators for endometrial cancer. Our findings also suggest that patients with positive peritoneal cytology in the absence of other adverse prognostic factors do not need upstaging.     

Mitochondrial polymorphisms as risk factors for endometrial cancer in southwest China

It is just in recent years that mitochondrial DNA (mtDNA) mutations have been found in solid tumors. Although a direct link between the presence of mtDNA mutations and the development of tumors has not been made, mtDNA mutations might prove significant in the detection of tumor recurrence and possibly in the detection of genotoxic damage. To investigate the relationship between mtDNA variation and endometrial cancer, we collected blood samples from subjects with Han native background in Yunnan province in China, 49 of them with pathologically conformed endometrial cancer and 31 as controls with no cancer disease and sequenced two hypervariable segments of control region, part of 16sRNA gene, tRNA(leu) (tRNA is transfer RNA) gene and ND1 gene of mtDNA and identified some diagnostic polymorphisms by restriction fragment length polymorphism of coding region of mtDNA. We could not identify the suspected mutations that are related to diabetes and obesity from our endometrial cancer patients. However, our data showed that patients with endometrial cancers clustered in haplogroup D in a significantly higher frequency when compared with controls, implicating a possible association of haplogroup D to endometrial cancer. We concluded that mitochondrial polymorphisms in haplogroup D might play a genetic role in predisposing to endometrial cancer.     

The effects of obesity and HER-2 polymorphisms as risk factors for endometrial cancer in Korean women

Objective  To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene, body mass index (BMI) and the risk of endometrial cancer.
Design  Case–control study.
Setting  Medical centres in Korea.
Sample  DNA samples and medical histories were obtained from 125 endometrial cancer cases and 302 controls.
Methods  The genotypes evaluated in HER-2 at positions –423, –655, –776, –857, –1170, –1177, –1253 of the coding region and two SNPs located in an intron by SNP-IT assay using SNPstream Ultra–high throughput system.
Main outcome measures  Odd ratio for endometrial cancer associated with HER-2 polymorphisms and BMI.
Results  Cases had a significantly higher BMI than controls and the obese subjects had a 2.65-fold increased risk for endometrial cancer. However, HER-2 polymorphism was not associated significantly with the risk of endometrial cancer. Subjects with BMI ≥ 25 kg/m² who carried rs1801200 AA, rs1801200 GA/GG, rs1810132 CT/CC, rs2517951 CT/TT and rs1058808 CG/GG genotype had significantly increased risk of endometrial cancer than subjects with a normal BMI ( P for linear trend <0.05). However, the risk in the subjects with the variant allele for HER-2 genotypes did not differ significantly compared to those with homozygous wild-type allele within specific BMI subgroups.
Conclusions  Endometrial cancer risk increased significantly in proportion to BMI. However, HER-2 polymorphism did not affect significantly on the risk of endometrial cancer.     

Risk factors for young premenopausal women with endometrial cancer

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5-30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women. METHODS: We conducted a retrospective cohort study of patients with histologically confirmed endometrial cancer treated at the University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical characteristics including age, body mass index (BMI), parity, diabetes, and personal or family history of cancer were obtained from the medical record. Pathologic information was obtained from pathology reports. RESULTS: Twelve percent (188/1531) of all patients with endometrial adenocarcinoma were aged younger than 50 years. The mean age at diagnosis was 41 years (range 21-49 years). Mean BMI was 34 kg/m(2) (range 18-68); 58% of patients had a BMI of 30 or greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six patients (19%) had synchronous ovarian cancers. CONCLUSION: We found that the majority of patients diagnosed with endometrial cancer at a young age were obese and nulliparous. In addition, we found a high incidence of synchronous primary ovarian cancers in this cohort of young, premenopausal women.     

The relation between age, time since menopause, and endometrial cancer in women with postmenopausal bleeding

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1-3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00-1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.     

Denser trabecular bone in women with endometrial carcinoma

Bone mineral density (BMD) was measured in the distal radius of patients with endometrial carcinoma (EC). The patients were classified into two subgroups depending on whether earlier hormonal replacement therapy (HRT) was given. Two groups of women were recruited as controls: patients with post-menopausal bleeding for non-malignant reasons (hospital controls) and healthy women, free of gyn-ecologic symptoms (non-hospital controls). The BMD was significantly higher in the cancer patients and also in the hospital controls than in the non-hospital controls. When several possible confounding factors were checked for in a multivariate analysis, BMD still differed between the groups. This could lend support to the hypothesis that patients with EC may have an altered endogenous endocrine status which eventually affects their bone mass. The results also stress the importance of using strictly defined, healthy women as controls.     

Risk factors for different histological types of ovarian cancer

Various histological types of ovarian cancer may develop from different etiological aspects. Data separated by histological subtypes collected in the framework of a large case-control study on ovarian cancer conducted in Italy were analyzed. The cases were women below the age of 75 years, admitted to a network of hospitals in Milan. Cases were grouped into four categories by histological type: mucinous tumor (n = 52), serous tumor (n = 680), endometrioid tumor (n = 41), and other histologies including clear-cell and undifferentiated epithelial tumors (n = 50). Controls were 2758 patients admitted to the same network of hospitals for a wide spectrum of acute, nongynecological, non-hormone-related, non-neoplastic conditions. In comparison with nulliparae, the risk of serous, endometrioid, and other histologies of ovarian cancer tended to be lower in parous women, but the odds ratios (OR) were above unity for mucinous ovarian cancer. Oral contraceptive use was associated with OR lower than unity for serous (OR = 0.7) and endometrioid (OR = 0.8) ovarian cancers but not for mucinous (OR = 1.4) and other histologies (OR = 1.6). Finally, our results on dietary fat intake did not show substantial differences in all histological types of ovarian cancer.     

The detection of microsatellite instability in blind endometrial samples—a potential novel screening tool for endometrial cancer in women from hereditary nonpolyposis colorectal cancer families?

Microsatellite instability (MSI) is the phenotypic molecular characteristic of the majority of tumors associated with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC). Women in this group have an increased risk of endometrial cancer (EC). This study aimed to determine whether MSI could be demonstrated in blind endometrial samples from women with EC, HNPCC kindreds undergoing screening for EC, and women with normal endometrium. Twenty-four women with EC, 20 women from HNPCC kindreds, and 20 women undergoing gynecological surgery for benign indications underwent blind sampling. MSI analysis was performed by conventional polymerase chain reaction using fluorescent-labeled primers and automated analysis. Twelve microsatellites were studied with MSI defined as evident when novel alleles were seen in endometrial biopsy samples compared to genomic DNA. Of the 24 EC samples obtained, sufficient DNA for analysis was extracted in 17 cases. Three cases had evidence of MSI in at least 7/12 loci. None of the endometrium from the two other study groups revealed evidence of MSI. This is the first demonstration of MSI in blind endometrial biopsies. The ability to demonstrate MSI in heterogeneous endometrial samples suggests potential for the development of a novel EC screening tool for women in HNPCC kindreds.     

子宫内膜采集器在子宫内膜癌及癌前病变筛查中的应用

目的探讨子宫内膜采集器应用于子宫内膜癌及癌前病变筛查时的准确性和可行性。方法 2012年4月至2012年11月北京大学人民医院妇科收治需行宫腔镜检查的患者131例。应用子宫内膜采集器采集子宫内膜组织,随后应用宫腔镜评价标本采集范围并直视下活检内膜组织。分别组织学制片后,对比二者的病理学结果,并计算敏感性,特异性和准确率。结果满意标本采集率83.21%(109/131)。满意标本109例,其中子宫内膜癌/不典型增生14例,检出13例,采集器筛查的敏感性和特异性分别为92.9%和100.00%,准确率为99.1%。取材不满意的22例患者中,6例(4.58%)组织过少,无法制片。16例(12.21%)擦痕不能遍布整个宫腔,其中11例为双侧输卵管开口处不能见到擦痕,5例为未能进入宫腔。结论子宫内膜采集器可以用来筛查子宫内膜癌及不典型增生;但不适合用于黏膜下子宫肌瘤和子宫内膜息肉的标本采集;需扩大样本量做进一步检验。     

化疗在晚期和复发性耐药性子宫内膜癌治疗中的作用

晚期和复发性耐药性子宫内膜癌预后差,化疗在子宫内膜癌治疗中具有越来越重要的价值。新辅助化疗、序贯放化疗、分子靶向药物如贝伐单抗等是目前治疗子宫内膜癌的研究热点,紫杉醇联合卡铂和蒽环类药物联合铂类是一线化疗药物方案。复发性耐药性子宫内膜癌治疗尚无成熟方案,仍需大样本临床试验验证。