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Sample records for high risk endometrial

  1. Identifying High-Risk Women for Endometrial Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk Prediction Model.

    Science.gov (United States)

    Kitson, Sarah J; Evans, D Gareth; Crosbie, Emma J

    2017-01-01

    Already the fourth most common cancer in women in the developed world, the incidence of endometrial cancer is increasing rapidly, in line with the increasing prevalence of obesity. Relatively few studies have been undertaken of risk-reducing interventions aimed at limiting the impact of the disease on both individuals and the health service. Those that have been performed have demonstrated only modest results due to their application in relatively unselected populations. A validated risk prediction model is therefore urgently required to identify individuals at particularly high risk of endometrial cancer who may benefit from targeted primary prevention strategies and to guide trial eligibility. On the basis of a systematic review of the literature, the evidence for inclusion of measures of obesity, reproduction, insulin resistance, and genetic risk in such a model is discussed, and the strength of association between these risk factors and endometrial cancer is used to guide the development of a pragmatic risk prediction scoring system that could be implemented in the general population. Provisional cutoff values are described pending refinement of the model and external validation in large prospective cohorts. Potential risk-reducing interventions are suggested, highlighting the need for future studies in this area if the increasing tide of endometrial cancer is to be stemmed. Cancer Prev Res; 10(1); 1-13. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients

    DEFF Research Database (Denmark)

    Antonsen, Sofie Leisby; Loft, Annika; Fisker, Rune Vincents

    2013-01-01

    OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical...... endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p...

  3. High-Grade Squamous Intraepithelial Lesion Cytology With Negative High-Risk Human Papillomavirus Tests Rarely Diagnoses Endometrial Cancer.

    Science.gov (United States)

    Pretorius, Robert G; Peterson, Patricia

    2015-07-01

    We hypothesized that women with cervical cytologic results of high-grade squamous intraepithelial lesion (HSIL) and negative high-risk human papillomavirus (HR-HPV) test results would have a high risk of having endometrial cancer and would benefit from routine endometrial biopsy. Reports of women with cytologic results of HSIL and negative HR-HPV test results were found in an electronic colposcopy database; their charts were reviewed. Rates of endometrial cancer for cytologic results of HSIL and negative HR-HPV test results were compared to a historical series for cytologic results of HSIL with positive HR-HPV and cytologic results of atypical glandular cells (AGCs) and negative HR-HPV test results. Between August 10, 1998, and April 20, 2013, 56 women were evaluated in our colposcopy clinics for cytologic results of HSIL and negative HR-HPV test results; of these 56 women, 1 (1.8%) was diagnosed with endometrial cancer. No endometrial cancer was diagnosed during the follow-up (median = 63 mo) after colposcopy. The risk for endometrial cancer with cytologic results of HSIL and negative HR-HPV test results (1.8%, 1/56) did not differ from that of a historical series from 2007 to 2009 from the same colposcopy clinic in 223 women with cytologic results of HSIL and positive HR-HPV test results (0.0%, 0/223; p = .2) and was lower than the risk for endometrial cancer from the historical series from 2007 to 2009 in women with cytologic results of AGC and negative HR-HPV test results (14.4%, 4/27; p = .04). Women with cytologic results of HSIL and negative HR-HPV test results are more like those with cytologic results of HSIL and positive HR-HPV test results than those with cytologic results of AGC and negative HR-HPV test results and would unlikely to benefit from routine endometrial biopsy at the time of colposcopy.

  4. Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients.

    Science.gov (United States)

    Eggink, F A; Mom, C H; Boll, D; Ezendam, N P M; Kruitwagen, R F P M; Pijnenborg, J M A; van der Aa, M A; Nijman, H W

    2017-08-01

    Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Hormonal Contraceptives for Endometrial Cancer Prevention in Obese and High-Risk Women in Virginia.

    Science.gov (United States)

    Horst, Kyle E; Modesitt, Susan C

    2016-10-01

    Endometrial cancer remains the fourth most common malignancy among US women, and hormonal contraceptives drastically reduce this risk. The study objectives were to assess the prescribing patterns, counseling practices, and knowledge of family physicians and obstetrician/gynecologists (OB/GYNs) regarding hormonal contraceptives, obesity, and cancer prevention. A 25-question survey was mailed to 4600 OB/GYNs and family practitioners licensed in Virginia to assess self-reported hormonal contraceptive prescription practices, patient evaluation and counseling, and gynecologic oncology knowledge. χ(2) and t tests were used to assess for differences across groups. P endometrial cancer risk associated with oral contraceptive pills (73.0%) and increased risk with obesity (95.3%), but only 36.7% consistently counseled patients on obesity-associated cancer risk. Compared with family physicians, OB/GYNs were more likely to cite endometrial cancer prevention as an indication for hormonal contraceptives (53.3% vs 10.9%, P obesity-related cancer risk (P = 0.003); and were more likely to correctly identify Lynch syndrome (69.4% vs 22.5%, P endometrial cancer. Endometrial or ovarian cancer prevention factored into endometrial cancer risk factors and the use of hormonal contraception for chemoprevention. This represents a significant opportunity for both specialties to optimize primary endometrial cancer prevention in their increasingly obese and at-risk female patients.

  6. Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico.

    Science.gov (United States)

    Salazar-Martinez, E; Lazcano-Ponce, E C; Gonzalez Lira-Lira, G; Escudero-De los Rios, P; Salmeron-Castro, J; Hernandez-Avila, M

    1999-08-01

    A case-control study was carried out in Mexico City during 1995-1997 among women with epithelial ovarian cancer (84 cases) and endometrial cancer (85 cases). The control group consisted of 668 healthy women, matched according to age categories. In a multivariate analysis, the reproductive risk factors for ovarian and endometrial cancer are similar. The risk of ovarian cancer was inversely related to the number of full-term pregnancies; the odds ratio (OR) was 0.17 and the 95% confidence interval (CI) was 0.05-0.54 when comparing nulliparous women versus those with more than seven pregnancies. For endometrial cancer, a similar association was observed (OR, 0.11; 95% CI, 0.04-0.34). The use of oral contraceptive hormones was inversely associated with both ovarian (OR, 0.36; 95% CI, 0.15-0.83) and endometrial cancer risk (OR, 0.36; 95% CI, 0.14-0.90). In women with a history of more than 8.7 years without ovulation, the risk of ovarian cancer decreased four times (OR, 0.23; 95% CI, 0.10-0.50), and that of endometrial cancer decreased more than five times (OR, 0.17; 95% CI, 0.08-0.35). These two neoplasms are clearly typified as hormone dependent, and it is possible to establish that "ovulation" and "exfoliative" mechanisms jointly determine the level of risk for both ovarian and endometrial cancer.

  7. Risk factors for developing endometrial cancer after benign endometrial sampling.

    Science.gov (United States)

    Torres, Michelle L; Weaver, Amy L; Kumar, Sanjeev; Uccella, Stefano; Famuyide, Abimbola O; Cliby, William A; Dowdy, Sean C; Gostout, Bobbie S; Mariani, Andrea

    2012-11-01

    To identify risk factors for endometrial cancer after benign results of endometrial biopsy or dilation and curettage (D&C). Nested case-control study from Rochester Epidemiology Project data. Among 370 Olmsted County, Minnesota, residents who received an endometrial cancer diagnosis between 1970 and 2008, we identified 90 patients (24.5%) who had previous benign endometrial biopsy or D&C results (no atypical hyperplasia). We compared them with 172 matched control group participants who had benign endometrial biopsy or D&C results without subsequent endometrial cancer. Using a multivariable conditional logistic regression model, we found that oral contraceptive pill (OCP) use was protective (odds ratio [OR] 0.18, 95% CI [CI] 0.08-0.45; Pmorbid obesity (OR 3.40, 95% CI 1.18-9.78; Prisk factor, presence of one and two or more risk factors increased the risk of endometrial cancer by 8.12 (95% CI 3.08-21.44) and 17.87 (95% CI 5.57-57.39) times, respectively. Assuming a 2.6% lifetime risk of endometrial cancer, ORs of 8.12 and 17.87 for one and two or more of the four aforementioned risk factors confer a lifetime risk of approximately 18% and 32%, respectively. One fourth of patients with endometrial cancer had previous benign endometrial biopsy or D&C results. Personal history of colorectal cancer, presence of endometrial polyps, and morbid obesity are the strongest risk factors for having endometrial cancer after a benign endometrial biopsy or D&C result, and OCP use is the strongest protective factor. II.

  8. Risks of Endometrial Cancer Screening

    Science.gov (United States)

    ... Treatment Endometrial Cancer Prevention Endometrial Cancer Screening Research Endometrial Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Endometrial Cancer Key Points Endometrial cancer is a disease ...

  9. Clinical outcomes of image guided radiation therapy (IGRT) with gold fiducial vaginal cuff markers for high-risk endometrial cancer

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    Monroe, Alan T.; Peddada, Anuj V. [Dept. of Radiation Oncology, Penrose Cancer Center, Colorado Springs (United States); Pikaart, Dirk [Dept. of Gynecologic Oncology, Penrose Cancer Center, Colorado Springs (United States)

    2013-06-15

    Objective. To report two year clinical outcomes of image guided radiation therapy (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk endometrial cancer patients. Methods . Twenty-six consecutive high-risk endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and regional lymph nodes were treated with vaginal cuff fiducial-based IGRT. Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich technique. Brachytherapy followed external radiation in 11 patients to a median dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy in 25 fractions. Results. All 656 fractions were successfully imaged and treated. The median overall translational shift required for correction was 9.1 mm (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos. Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in eight patients (30%) and grade 3 toxicity occurred in one. At two years, there have been no local or regional failures and actuarial overall survival is 95%. Conclusion. Daily image guidance for high-risk endometrial cancer results in a low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor control at two years. Vaginal cuff translations can be substantial and may possibly result in underdosing if not properly considered.

  10. Patterns of care and the survival of elderly patients with high-risk endometrial cancer: A case-control study from the FRANCOGYN group.

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    Rousselin, A; Bendifallah, S; Nyangoh Timoh, K; Ouldamer, L; Canlorbe, G; Raimond, E; Hudry, N; Coutant, C; Graesslin, O; Touboul, C; Collinet, P; Bricou, A; Huchon, C; Daraï, E; Ballester, M; Levêque, J; Lavoue, V

    2017-11-01

    The standard of care of endometrial cancer involves complex procedures such as pelvic and para-aortic lymphadenectomy and omentectomy, particularly for high-risk endometrial cancer. Few data are available about these complex surgical procedures and adjuvant therapy in elderly women. We aim to examine treatment and survival of elderly women diagnosed with high-risk endometrial cancer. We performed a case-control study of women diagnosed between 2001 and 2013 with high-risk endometrial cancers. Women older than 70 years (n = 198) were compared with patients Elderly patients had lymphadenectomies less frequently compared with younger patients (76% vs 96%, p elderly women had 57% increased risk of recurrence (hazard ratio 1.57, 95% CI 1.04-2.39) compared with younger patients. Although we found an independently significant lower DFS in elderly patients with high-risk endometrial cancer when compared with young patients, elderly women are less likely to be treated with lymphadenectomy and chemotherapy. Specific guidelines for management of elderly patients with high-risk endometrial cancer are required to improve their prognosis. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  11. Oral contraception and risk of endometrial cancer

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    Mueck AO

    2011-10-01

    , especially in patients with a high risk of cancer, as in polycystic ovary disease, and should also include new contraceptive drugs using natural estradiol instead of ethinyl estradiol. Of importance is the question of the potency of hormonal intrauterine devices to protect against endometrial cancer. It can be concluded on the basis of biological plausibility and observational data that COC can strongly decrease the risk of estrogen-related endometrial cancer, with an effect persisting after withdrawal of the hormones, and a causal relationship for this protection against cancer seems reasonable. Keywords: hormonal contraceptives, endometrial cancer

  12. High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian Women and Cancer Study: a population-based prospective study

    Science.gov (United States)

    2014-01-01

    Background Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. Methods A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. Results During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. Conclusions These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method. PMID:24666820

  13. Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition

    NARCIS (Netherlands)

    Eggink, Florine A.; Van Gool, Inge C.; Leary, Alexandra; Pollock, Pamela M.; Crosbie, Emma J.; Mileshkin, Linda; Jordanova, Ekaterina S.; Adam, Julien; Freeman-Mills, Luke; Church, David N.; Creutzberg, Carien L.; De Bruyn, Marco; Nijman, Hans W.; Bosse, Tjalling

    2017-01-01

    High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs

  14. HIGH COLORECTAL AND LOW ENDOMETRIAL CANCER RISK IN EPCAM DELETION-POSITIVE LYNCH SYNDROME: A COHORT STUDY

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    Kempers, Marlies JE; Kuiper, Roland P; Ockeloen, Charlotte W; Chappuis, Pierre O; Hutter, Pierre; Rahner, Nils; Schackert, Hans K; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Büttner, Reinhard; Verwiel, Eugene TP; van Krieken, J. Han; Nagtegaal, Iris D; Goossens, Monique; van der Post, Rachel S.; Niessen, Renée C; Sijmons, Rolf H; Kluijt, Irma; Hogervorst, Frans BL; Leter, Edward M; Gille, Johan JP; Aalfs, Cora M; Redeker, Egbert JW; Hes, Frederik J; Tops, Carli MJ; van Nesselrooij, Bernadette PM; van Gijn, Marielle E; García, Encarna B Gómez; Eccles, Diana M; Bunyan, David J; Syngal, Sapna; Stoffel, Elena M; Culver, Julie O; Palomares, Melanie R; Graham, Tracy; Velsher, Lea; Papp, Janos; Oláh, Edith; Chan, Tsun L; Leung, Suet Y; van Kessel, Ad Geurts; Kiemeney, Lambertus ALM; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn JL

    2013-01-01

    Summary BACKGROUND Lynch syndrome is caused by germline mutations in mismatch repair genes (MSH2, MLH1, MSH6 or PMS2), which lead to a high risk of predominantly colorectal and endometrial cancer. Recently, we found that also constitutional 3′ end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM expressing tissues. This results in a tissue specific MSH2-deficiency, which may evoke a different cancer risk and spectrum. To optimize the care for EPCAM deletion carriers we studied their cancer risk and spectrum. METHODS Clinical data of 194 carriers from 41 EPCAM families were systematically collected and compared to those of 431 carriers from 91 families with mutations in MLH1, MSH2, or MSH6. FINDINGS EPCAM deletion carriers exhibited a 75% [95%CI 65–85%] cumulative risk of colorectal cancer before the age of 70 years, with a mean age at diagnosis of 43 years, which is comparable to that of carriers of a combined EPCAM-MSH2 deletion (69% [95%CI 47-91%], p=0·8609) or of a mutation in MSH2 (77% [95%CI 64-90%], p=0·5892) or MLH1 (79% [95%CI 68-90%], p=0·5492) and higher than that of MSH6 mutation carriers (50% [95%CI 38-62%], p<0·0001). In contrast, women with EPCAM deletions (n=87) exhibited a 12% [95%CI 0-27%] cumulative risk of endometrial cancer, which is significantly lower than in carriers of a combined EPCAM-MSH2 deletion (55% [95%CI 20-90%], p<0·0001) or of a mutation in MSH2 (51% [95%CI 33-69%], p=0·0006) or MSH6 (34% [95%CI 20-48%], p=0·0309) and lower than in MLH1 (33% [95%CI 15-51%] p=0·1193) mutation carriers. This risk seems to be restricted to large deletions that extend close to the MSH2 gene promoter. Overall, a relatively high incidence of duodenal (n=3) and pancreatic (n=4) cancers was observed. INTERPRETATION EPCAM deletion carriers do have a high risk of colorectal cancer. Only those with deletions extending close to the MSH2 promoter have an increased risk of endometrial cancer. These results

  15. Long-term risk of endometrial cancer following postmenopausal bleeding and reassuring endometrial biopsy

    NARCIS (Netherlands)

    Visser, N.C.M.; Sparidaens, E.M.; Brink, J.W. van den; Breijer, M.C.; Boss, E.A.; Veersema, S.; Siebers, A.G.; Bulten, J.; Pijnenborg, J.M.A.; Bekkers, R.L.M.

    2016-01-01

    INTRODUCTION: Women with postmenopausal bleeding and endometrial thickness >4 mm undergo endometrial sampling to exclude endometrial cancer. The aim of this study is to investigate the relative risk of developing endometrial cancer in a prospective cohort after initial work-up for postmenopausal

  16. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3) : an open-label, multicentre, randomised, phase 3 trial

    NARCIS (Netherlands)

    de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Kitchener, Henry C.; Nijman, Hans W.; Kruitwagen, Roy F.; Nout, Remi A.; Verhoeven-Adema, Karen W.; Smit, Vincent T.; Putter, Hein; Creutzberg, Carien L.

    Background About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women

  17. Development and external validation of new ultrasound-based mathematical models for preoperative prediction of high-risk endometrial cancer.

    Science.gov (United States)

    Van Holsbeke, C; Ameye, L; Testa, A C; Mascilini, F; Lindqvist, P; Fischerova, D; Frühauf, F; Fransis, S; de Jonge, E; Timmerman, D; Epstein, E

    2014-05-01

    To develop and validate strategies, using new ultrasound-based mathematical models, for the prediction of high-risk endometrial cancer and compare them with strategies using previously developed models or the use of preoperative grading only. Women with endometrial cancer were prospectively examined using two-dimensional (2D) and three-dimensional (3D) gray-scale and color Doppler ultrasound imaging. More than 25 ultrasound, demographic and histological variables were analyzed. Two logistic regression models were developed: one 'objective' model using mainly objective variables; and one 'subjective' model including subjective variables (i.e. subjective impression of myometrial and cervical invasion, preoperative grade and demographic variables). The following strategies were validated: a one-step strategy using only preoperative grading and two-step strategies using preoperative grading as the first step and one of the new models, subjective assessment or previously developed models as a second step. One-hundred and twenty-five patients were included in the development set and 211 were included in the validation set. The 'objective' model retained preoperative grade and minimal tumor-free myometrium as variables. The 'subjective' model retained preoperative grade and subjective assessment of myometrial invasion. On external validation, the performance of the new models was similar to that on the development set. Sensitivity for the two-step strategy with the 'objective' model was 78% (95% CI, 69-84%) at a cut-off of 0.50, 82% (95% CI, 74-88%) for the strategy with the 'subjective' model and 83% (95% CI, 75-88%) for that with subjective assessment. Specificity was 68% (95% CI, 58-77%), 72% (95% CI, 62-80%) and 71% (95% CI, 61-79%) respectively. The two-step strategies detected up to twice as many high-risk cases as preoperative grading only. The new models had a significantly higher sensitivity than did previously developed models, at the same specificity. Two

  18. Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer : A TransPORTEC initiative

    NARCIS (Netherlands)

    Edmondson, R. J.; Crosbie, E. J.; Nickkho-Amiry, M.; Kaufmann, A.; Stelloo, E.; Nijman, H. W.; Leary, A.; Auguste, A.; Mileshkin, L.; Pollock, P.; MacKay, H. J.; Powell, M. E.; Bosse, T.; Creutzberg, C. L.; Kitchener, H. C.

    Background. The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53

  19. Compliance with adjuvant treatment guidelines in endometrial cancer : Room for improvement in high risk patients

    NARCIS (Netherlands)

    Eggink, F. A.; Mom, C. H.; Boll, D.; Ezendam, N. P. M.; Kruitwagen, R. F. P. M.; Pijnenborg, J. M. A.; van der Aa, M. A.; Nijman, H. W.

    Objectives. Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10 years. Methods.

  20. Intentional Weight Loss and Endometrial Cancer Risk.

    Science.gov (United States)

    Luo, Juhua; Chlebowski, Rowan T; Hendryx, Michael; Rohan, Thomas; Wactawski-Wende, Jean; Thomson, Cynthia A; Felix, Ashley S; Chen, Chu; Barrington, Wendy; Coday, Mace; Stefanick, Marcia; LeBlanc, Erin; Margolis, Karen L

    2017-04-10

    Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women's Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.

  1. Statin use and risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sperling, Cecilie D.; Verdoodt, Freija; Friis, Soren

    2017-01-01

    on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy......INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer....... MATERIAL AND METHODS: Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions...

  2. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

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    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  3. PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors.

    Science.gov (United States)

    Yang, Hannah P; Meeker, Alan; Guido, Richard; Gunter, Marc J; Huang, Gloria S; Luhn, Patricia; d'Ambrosio, Lori; Wentzensen, Nicolas; Sherman, Mark E

    2015-12-01

    Clonal loss of PTEN expression occurs frequently in endometrial carcinoma and endometrial hyperplasia. Limited data from immunohistochemical studies suggest that PTEN-null appearing endometrial glands are detectable in women without pathologic abnormalities, but the relationship of PTEN expression to endometrial cancer risk factors has not been extensively explored. We evaluated relationships between endometrial cancer risk factors and loss of PTEN expression in a set of benign endometrial samples prospectively collected from women undergoing hysterectomy and in endometrial cancer tissues from a population-based case-control study. We used a validated PTEN immunohistochemical assay to assess expression in epidemiological studies designed to assess benign endometrium [Benign Reproductive Tissue Evaluation Study (n = 73); Einstein Endometrium Study (n = 19)], and endometrial cancer [Polish Endometrial Cancer Study (n = 148)] tissues. Associations between endometrial cancer risk factors (collected via study-specific risk factor questionnaires) and PTEN expression in endometrial tissues were determined using Fisher's exact tests. PTEN loss was detected in 19% of benign endometrial tissues versus 55% in endometrial cancers. NSAID use was statistically significantly associated with PTEN loss in the benign endometrium (p = 0.02). Our data demonstrate that PTEN loss is detectable in endometrial tissues that are benign and malignant, with substantially more frequent loss in endometrial cancer compared with benign endometrium. However, alterations in expression were unrelated to most risk factors in this analysis, except for the association with NSAID use, which may represent a chance finding or reverse causality among patients with endometriosis who may have PTEN pathway abnormalities in eutopic endometrium. Further evaluation of factors associated with PTEN loss and long-term follow-up of women with PTEN-null endometrial glands may be useful in understanding early events

  4. [Relationship of endometrial thickness and endometrial cancer risk in postmenopausal women].

    Science.gov (United States)

    Li, L; Wu, M

    2017-07-23

    Evaluation of the vaginal bleeding of postmenopausal women is crucial to diagnose endometrial lesions. Endometrial thickness measured by transvaginal ultrasonography provides an important reference for diagnosis. Currently, no specific cut-off value of endometrial thickness has been identified to predict the malignant risk for endometrial thickening and postmenopausal women without any symptoms. Most of resected endometrial specimens from postmenopausal women without any symptoms are diagnosed as benign or normal tissues. It seems that postmenopausal women without any symptoms have no need for general screen or intervention of endometrial cancer.

  5. Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative.

    Science.gov (United States)

    Edmondson, R J; Crosbie, E J; Nickkho-Amiry, M; Kaufmann, A; Stelloo, E; Nijman, H W; Leary, A; Auguste, A; Mileshkin, L; Pollock, P; MacKay, H J; Powell, M E; Bosse, T; Creutzberg, C L; Kitchener, H C

    2017-08-01

    The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63. About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed. Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease. Copyright © 2017. Published by Elsevier Inc.

  6. Body Mass Index Genetic Risk Score and Endometrial Cancer Risk.

    Science.gov (United States)

    Prescott, Jennifer; Setiawan, Veronica W; Wentzensen, Nicolas; Schumacher, Fredrick; Yu, Herbert; Delahanty, Ryan; Bernstein, Leslie; Chanock, Stephen J; Chen, Chu; Cook, Linda S; Friedenreich, Christine; Garcia-Closas, Monserrat; Haiman, Christopher A; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M; Olson, Sara H; Risch, Harvey A; Shu, Xiao-Ou; Ursin, Giske; Yang, Hannah P; Kraft, Peter; De Vivo, Immaculata

    2015-01-01

    Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10-5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.

  7. Body Mass Index Genetic Risk Score and Endometrial Cancer Risk.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Genome-wide association studies (GWAS have identified common variants that predispose individuals to a higher body mass index (BMI, an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002. For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%. However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78. Heterogeneity by BMI did not reach statistical significance (P = 0.06, and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58. In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10-5. Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.

  8. Diet and endometrial cancer: a focus on the role of fruit and vegetable intake, Mediterranean diet and dietary inflammatory index in the endometrial cancer risk.

    Science.gov (United States)

    Ricceri, Fulvio; Giraudo, Maria Teresa; Fasanelli, Francesca; Milanese, Dario; Sciannameo, Veronica; Fiorini, Laura; Sacerdote, Carlotta

    2017-11-13

    Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.

  9. Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk

    Science.gov (United States)

    Wang, Zhanwei; Risch, Harvey; Lu, Lingeng; Irwin, Melinda L.; Mayne, Susan; Schwartz, Peter; Rutherford, Thomas; De Vivo, Immaculata; Yu, Herbert

    2015-01-01

    Prolonged estrogen exposure is believed to be the major cause of endometrial cancer. As possible markers of estrogen exposure, various menstrual and reproductive features, e.g., ages at menarche and menopause, are found to be associated with endometrial cancer risk. In order to assess their combined effects on endometrial cancer, we created the total number of menstrual cycles (TNMC) that a woman experienced during her life or up to the time of study and two genetic risk scores, GRS1 for age at menarche and GRS2 for age at menopause. Comparing 482 endometrial cancer patients with 571 population controls, we found TNMC was associated with endometrial cancer risk and that the association remained statistically significant after adjustment for obesity and other potential confounders. Risk increased by about 2.5% for every additional 10 menstrual-cycles. The study also showed that high GRS1 was associated with increased risk. This relationship, however, was attenuated after adjustment for obesity. Our study further indicated women with high TNMC and GRS1 had twice the risk of endometrial cancer compared to those low in both indices. Our results provided additional support to the involvement of estrogen exposure in endometrial cancer risk with regard to genetic background and lifestyle features. PMID:26498156

  10. Non-steroidal anti-inflammatory drug use and risk of endometrial cancer

    DEFF Research Database (Denmark)

    Verdoodt, Freija; Friis, Søren; Dehlendorff, Christian

    2016-01-01

    OBJECTIVE: Non-steroidal anti-inflammatory drug (NSAID) use has been linked to a reduction in the risk of several cancer types. For endometrial cancer, however, results have been inconsistent. To summarize the available evidence on the risk of endometrial cancer associated with use of aspirin...... a random effects model. RESULTS: Six case-control and seven cohort studies were found eligible for our meta-analysis. We observed risk reductions in endometrial cancer associated with regular use of aspirin (case-control: 11%, cohort: 8%) and NA-NSAIDs (case-control: 9%, cohort: 6%), compared to non......-use. However, the pooled risk ratios were not statistically significant. Higher risk reductions were seen with high frequency of notably aspirin use (case-control: 37%, cohort: 20%). The inverse association between regular aspirin use and endometrial cancer risk was strongest among women with a body mass index...

  11. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

    Science.gov (United States)

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-08-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. Distribution of the 729 women with EC according to BMI was BMI obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

  12. Aspirin use and endometrial cancer risk and survival.

    Science.gov (United States)

    Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

    2018-01-01

    The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Obesity, lymphadenectomy and survival outcomes in intermediate to high-risk, early-stage endometrial cancer patients.

    Science.gov (United States)

    Linkov, Faina; Edwards, Robert P; Althouse, Andrew; Rauh-Hain, Jose A; Del Carmen, Marcela G; Freese, Kyle E; Kelley, Joseph L; Olawaiye, Alexander B

    2015-01-01

    Lymphadenectomy or lymph node dissection is a topic of controversy in endometrial cancer (EC) treatment. Associations between lymph node dissections and clinical factors were retrospectively examined in obese, endometrioid endometrial cancer patients with early-stage disease between 1995 and 2005. Overall, EC-specific and recurrence-free survival were also evaluated. Out of 192 patients, 61 (32%) did not have a lymph node examination, 55 (29%) had less than ten lymph nodes removed and 76 (39%) had ≥10 removed. Lymph node dissection count was not significantly associated with overall, EC-specific or recurrence-free survival. Analysis revealed no significant associations between ≥10 dissected lymph nodes and survival outcomes among obese, EC patients, which supports the need for additional investigation of the merit of lymphadenectomy among these patients.

  14. Dietary carbohydrate intake, glycemic index, and glycemic load and endometrial cancer risk: a prospective cohort study.

    Science.gov (United States)

    Coleman, Helen G; Kitahara, Cari M; Murray, Liam J; Dodd, Kevin W; Black, Amanda; Stolzenberg-Solomon, Rachael Z; Cantwell, Marie M

    2014-01-01

    Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95% confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95% CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.

  15. Hormone replacement therapy and the risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sjögren, Lea L; Mørch, Lina Steinrud; Løkkegaard, Ellen

    2016-01-01

    , estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone......BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus...... progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only...

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

    Science.gov (United States)

    Tong, S-Y; Ha, S-Y; Ki, K-D; Lee, J-M; Lee, S-K; Lee, K-B; Kim, M-K; Cho, C-H; Kwon, S-Y

    2009-07-01

    To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene, body mass index (BMI) and the risk of endometrial cancer. Case-control study. Medical centres in Korea. DNA samples and medical histories were obtained from 125 endometrial cancer cases and 302 controls. 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. Odd ratio for endometrial cancer associated with HER-2 polymorphisms and BMI. 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 > or = 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 Endometrial cancer risk increased significantly in proportion to BMI. However, HER-2 polymorphism did not affect significantly on the risk of endometrial cancer.

  17. Association of dietary glycemic index and glycemic load with endometrial cancer risk among Chinese women

    Science.gov (United States)

    Xu, Wang Hong; Xiang, Yong-Bing; Zhang, Xianglan; Ruan, Zhixian; Cai, Hui; Zheng, Wei; Shu, Xiao-Ou

    2017-01-01

    We evaluated the association of dietary glycemic-index (GI) and glycemic-load (GL) with the risk of endometrial cancer in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 age-frequency-matched controls in urban Shanghai, China, where diets are typically high in carbohydrates and have a high GL. Information on dietary habits, physical activity, and other relevant information was collected using a validated questionnaire, and anthropometric measurements were taken. Logistic regression was applied in the analysis. Dietary GI was independently associated with risk for endometrial cancer but GL and carbohydrate intake was unrelated to the risk. Multivariable-adjusted odds ratios (ORs) for increasing quartiles of intake were 1.0, 1.2, 1.4, and 1.4 (95% CI: 1.0–2.0) for dietary GI (Ptrend: 0.07). High intake of staples, especially rice, was positively associated with endometrial cancer. The association with GI was more evident among lean and normal weight women, although the test for interaction was not significant. This study suggests that intake of high GI foods, but not carbohydrates per se, may increase risk for endometrial cancer. PMID:25495185

  18. Association of dietary glycemic index and glycemic load with endometrial cancer risk among Chinese women.

    Science.gov (United States)

    Xu, Wang Hong; Xiang, Yong-Bing; Zhang, Xianglan; Ruan, Zhixian; Cai, Hui; Zheng, Wei; Shu, Xiao-Ou

    2015-01-01

    We evaluated the association of dietary glycemic index (GI) and glycemic load (GL) with the risk of endometrial cancer in a population-based, case-control study of 1199 endometrial cancer patients and 1212 age-frequency-matched controls in urban Shanghai, China, where diets are typically high in carbohydrates and have a high GL. Information on dietary habits, physical activity, and other relevant information was collected using a validated questionnaire, and anthropometric measurements were taken. Logistic regression was applied in the analysis. Dietary GI and GL were independently associated with risk for endometrial cancer but carbohydrate intake was unrelated to risk. Multivariable-adjusted odds ratios (ORs) for increasing quartiles of intake were 1.0, 1.3, 1.4, and 2.2 [95% confidence interval (CI): 1.2-4.0] for dietary GL (P(trend) = 0.02) and 1.0, 1.2, 1.4, and 1.4 (95% CI: 1.0-2.0) for dietary GI (P(trend) = 0.02). High intake of staples, especially rice, was positively associated with endometrial cancer. The association with GI was more evident among lean and normal weight women, although the test for interaction was not significant. This study suggests that intake of high GL or GI foods, but not carbohydrates per se, may increase risk for endometrial cancer.

  19. Obesity risk awareness in women with endometrial cancer.

    Science.gov (United States)

    Connor, Elizabeth V; Raker, Christina A; Clark, Melissa A; Stuckey, Ashley R

    2017-04-01

    To assess whether women with endometrial cancer could accurately classify their weight and identify the association between obesity and risk of endometrial, breast, and colon cancers. This was an IRB-approved (Project No. 14-0075), survey-based cross-sectional study of women ages 18-80 years with a diagnosis of endometrial cancer. Patients were at least 6 months from hysterectomy and 3 months from chemotherapy or radiation. Statistical analysis was completed using Fisher's exact test, T test, ANOVA, Wilcoxon rank-sum test, or Kruskal-Wallis test. P values were two-tailed with P obese, compared to 32.0% of women with BMI 35.0-39.99 kg/m(2), and 72.7% of women with BMI >40.0 kg/m(2). Ability to correctly classify weight correlated significantly with education level (P = 0.02). Less than half of women identified obesity as a risk factor for breast (49.6%), colon (48.1%), and endometrial cancer (44.4%). 77% of all patients had discussed weight with their primary care doctor, and 38% had discussed weight with their oncologist (P obese women with endometrial cancer surveyed were unable to accurately classify their weight. Given the inconsistency between patient weight and perception of cancer risk, this represents an opportunity for gynecologic oncologists to educate their patients about weight control.

  20. A prospective study of dietary acrylamide intake and the risk of breast, endometrial, and ovarian cancers

    Science.gov (United States)

    Wilson, Kathryn M.; Mucci, Lorelei A.; Rosner, Bernard A.; Willett, Walter C.

    2010-01-01

    Background Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiological studies of acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk of breast, endometrial, and ovarian cancers in a prospective cohort study. Methods We assessed acrylamide intake among 88,672 women in the Nurses’ Health Study using food frequency questionnaires administered every four years. Between 1980 and 2006 we identified 6301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk. Results We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk of endometrial cancer among high acrylamide consumers (adjusted relative risk [RR] for highest versus lowest quintile=1.41, 95% CI: 1.01–1.97, p-value for trend=0.03). We observed a non-significant suggestion of increased risk for ovarian cancer overall (RR 1.25, CI: 0.88–1.77, p-trend=0.12), with a significantly increased risk for serous tumors (RR 1.58, CI: 0.99–2.52, p-trend=0.04). Associations did not differ by smoking status. Conclusions We observed no association between acrylamide and breast cancer. Risk of endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers. Impact This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy. PMID:20693310

  1. Understanding obesity and endometrial cancer risk: opportunities for prevention.

    Science.gov (United States)

    Schmandt, Rosemarie E; Iglesias, David A; Co, Ngai Na; Lu, Karen H

    2011-12-01

    Worldwide, obesity has become a major public health crisis. Overweight and obesity not only increase the risk of cardiovascular disease and type-2 diabetes mellitus but also are now known risk factors for a variety of cancer types. Among all cancers, increasing body mass index is associated most strongly with endometrial cancer incidence and death. The molecular mechanisms underlying how adipose tissue and obesity contribute to the pathogenesis of endometrial cancer are becoming better understood and have revealed a number of rational strategies, both behavioral and pharmaceutical, for the prevention of both primary and recurrent disease. Copyright © 2011. Published by Mosby, Inc.

  2. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis.

    Science.gov (United States)

    Li, Zhi-Jun; Yang, Xue-Ling; Yao, Yan; Han, Wei-Qing; Li, B O

    2016-06-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were -1.96 (-2.60, -1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (-0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (-0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of -2.27 (-4.36, -0.18) and P0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer.

  3. High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer.

    Directory of Open Access Journals (Sweden)

    John J Wallbillich

    Full Text Available STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin.In Ishikawa (grade 1 endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR. Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin.Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins.These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin.

  4. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Hanbyoul [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, Byung-Ho [Cancer Biostatistics Branch, Research Institute for National Cancer Control and Evaluation, National Cancer Center, Goyang (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Cho, Chi-Heum [Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Byoung Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Hee-Sug [Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon (Korea, Republic of); Kang, Soon Beom [Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Kim, Jae-Hoon, E-mail: jaehoonkim@yuhs.ac [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

  5. Anthropometric measures and the risk of endometrial cancer, overall and by tumor microsatellite status and histological subtype.

    Science.gov (United States)

    Amankwah, Ernest K; Friedenreich, Christine M; Magliocco, Anthony M; Brant, Rollin; Courneya, Kerry S; Speidel, Thomas; Rahman, Wahida; Langley, Annie R; Cook, Linda S

    2013-06-15

    Obesity is an established risk factor for endometrial cancer, but this association is not well understood for subtypes of endometrial cancer. We evaluated the association of recent and adult-life obesity with subtypes of endometrial cancer based on microsatellite status (microsatellite-stable (MSS) vs. microsatellite-instable (MSI)) and histology (type I vs. type II). Analyses were based on a population-based case-control study (524 cases and 1,032 controls) conducted in Alberta, Canada (2002-2006) and included the following groupings of subtypes: MSS = 337 and MSI = 130; type I = 458 and type II = 66. Logistic and polytomous logistic regression were used to estimate odds ratios and 95% confidence intervals for overall endometrial cancer and subtypes of endometrial cancer, respectively. The risks of all subtypes of endometrial cancer, except type II, increased with an increase in all of the anthropometric characteristics examined. The risks for MSI tumors were suggestively stronger than those for MSS tumors; the risk with high (≥30) body mass index (weight (kg)/height (m)(2)) was significantly stronger for MSI tumors (odds ratio = 4.96, 95% confidence interval: 2.76, 8.91) than for MSS tumors (odds ratio = 2.33, 95% confidence interval: 1.66, 3.28) (P-heterogeneity = 0.02). Obesity is associated with most subtypes of endometrial cancer, and further studies are warranted to elucidate the biological mechanisms underlying the stronger risk for the MSI subtype with a high body mass index.

  6. Endometrial cancer risk prediction including serum-based biomarkers : results from the EPIC cohort

    NARCIS (Netherlands)

    Fortner, Renée T.; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H. Bas|info:eu-repo/dai/nl/06929528X; Peeters, Petra H M|info:eu-repo/dai/nl/074099655; Weiderpass, Elisabete; Gram, Inger T.; Gavrilyuk, Oxana; Quirós, J. Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay Tee; Allen, Naomi E.; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A.; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-01-01

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested

  7. A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Katherine A Bolton

    2016-06-01

    Full Text Available Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case–control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively, but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013. This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012. Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.

  8. Risk of endometrial cancer after tamoxifen treatment of breast cancer

    NARCIS (Netherlands)

    F.E. van Leeuwen (Flora); J. Benraadt (J.); J.W.W. Coebergh (Jan Willem); L.A.L.M. Kiemeney (Bart); C.H.F. Gimbrère (Charles); R. Otter (Renée); L.J. Scheuten (Leo); R.A. Damhuis (Ronald); M. Bontenbal (Marijke); A.I. Diepenhorst; A.W. van den Belt-Dusebout (Alexandra); H. van Tinteren (Harm)

    1994-01-01

    textabstractSince large trials have been set up to assess whether tamoxifen decreases the risk of breast cancer in healthy women, it has become important to investigate the drug's potential adverse effects, including occurrence of endometrial cancer. We undertook a case-control study in the

  9. Long-term impact of preeclampsia on maternal endometrial cancer risk

    DEFF Research Database (Denmark)

    Hallum, Sara; Pinborg, Anja; Kamper-Jørgensen, Mads

    2016-01-01

    BACKGROUND: Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. METHODS: We conducted a case-control study of 523 Danish women with endometrial cancer and 52 299controls during...... 1978-2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. RESULTS: We observed no overall association between preeclampsia and endometrial cancer risk...... (OR=1.11 (95% CI 0.68-1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29-5.38)). CONCLUSIONS: Although we report no obvious...

  10. Dietary Acrylamide and the Risk of Endometrial Cancer: An Italian Case-Control.

    Science.gov (United States)

    Pelucchi, Claudio; Galeone, Carlotta; Negri, Eva; Bosetti, Cristina; Serraino, Diego; Montella, Maurizio; Talamini, Renato; La Vecchia, Carlo

    2016-01-01

    The role of dietary acrylamide on the risk of hormone-related, and specifically endometrial, cancers is debated. Epidemiological data are scanty. Thus, we examined the relation between acrylamide intake and endometrial cancer risk in a case-control study conducted between 1992 and 2006 in 3 Italian areas. Cases were 454 women with incident, histologically confirmed endometrial cancer. Controls were 908 age-matched women admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. The OR of endometrial cancer for increasing quintiles of dietary acrylamide, as compared to the lowest one, were 1.02 (95% CI: 0.67-1.54), 1.20 (95% CI: 0.80-1.80), 1.00 (95% CI: 0.65-1.54) and 1.17 (95% CI: 0.73-1.85). The OR for an increase of 10 μg/day of dietary acrylamide was 1.00 (95% CI: 0.91-1.10). In subgroup analyses, the ORs for high vs. low acrylamide intake were 1.28 (95% CI: 0.73-2.25) in never smokers and 1.14 (95% CI: 0.45-2.90) in ever smokers. Our data do not support an association between dietary acrylamide intake and endometrial cancer.

  11. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome : a cohort study

    NARCIS (Netherlands)

    Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Chappuis, Pierre O.; Hutter, Pierre; Rahner, Nils; Schackert, Hans K.; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Buettner, Reinhard; Verwiel, Eugene T. P.; van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Niessen, Renee C.; Sijmons, Rolf H.; Kluijt, Irma; Hogervorst, Frans B. L.; Leter, Edward M.; Gille, Johan J. P.; Aalfs, Cora M.; Redeker, Egbert J. W.; Hes, Frederik J.; Tops, Carli M. J.; van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.; Garcia, Encarna B. Gomez; Eccles, Diana M.; Bunyan, David J.; Syngal, Sapna; Stoffel, Elena M.; Culver, Julie O.; Palomares, Melanie R.; Graham, Tracy; Velsher, Lea; Papp, Janos; Olah, Edith; Chan, Tsun L.; Leung, Suet Y.; van Kessel, Ad Geurts; Kiemeney, Lambertus A. L. M.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.

    Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of

  12. Childhood body mass index growth trajectories and endometrial cancer risk.

    Science.gov (United States)

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate; Ulrich, Lian G; Sørensen, Thorkild I A; Baker, Jennifer L

    2017-01-15

    Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  13. Metabolic syndrome and risk of endometrial cancer in the united states: a study in the SEER-medicare linked database.

    Science.gov (United States)

    Trabert, Britton; Wentzensen, Nicolas; Felix, Ashley S; Yang, Hannah P; Sherman, Mark E; Brinton, Louise A

    2015-01-01

    Metabolic syndrome and its component feature, central obesity, are associated with endometrial cancer risk. It remains unclear whether associations with the other metabolic factors that comprise metabolic syndrome are independent of the obesity-endometrial cancer association. Furthermore, the link with specific endometrial cancer subtypes remains ill-defined, despite evidence of etiologic heterogeneity among these tumors. In a case-control study within the SEER-Medicare linked database, we examined whether metabolic factors, individually or combined, were associated with endometrial cancer. Cases (n = 16,323) were women diagnosed with endometrial cancer from 1993 through 2007. Controls (n = 100,751) were a 5% sample of female Medicare enrollees residing in the same SEER registry area as cases. Metabolic syndrome was defined using ICD-9-CM codes from inpatient/outpatient diagnoses 1 to 3 years before case diagnosis and a comparable time period in controls. ORs and 95% confidence intervals (CI) were estimated using logistic regression. Endometrial cancer risk was associated with metabolic syndrome [OR (95% CI): 1.39 (1.32-1.47)] and its component factors: overweight/obesity [1.95 (1.80-2.11)], impaired fasting glucose [1.36 (1.30-1.43)], high blood pressure [1.31 (1.25-1.36)], and high triglycerides [1.13 (1.08-1.18)]. After adjusting for overweight/obesity, the increased risks associated with the metabolic syndrome factors remained. Heterogeneity of associations by subtype were not identified (Pheterogeneity = 0.82). Among women age 65 and older in the United States, metabolic syndrome, and its component factors, increased endometrial cancer risk similarly across endometrial cancer subtypes. Strategies to reduce the prevalence of metabolic syndrome factors might have a favorable effect on endometrial cancer incidence. ©2015 American Association for Cancer Research.

  14. Predictors for lymph nodes involvement in low risk endometrial cancer.

    Science.gov (United States)

    Kadan, Yfat; Calvino, Abdul Saied; Katz, Andrew; Katz, Steven; Moore, Richard G

    2017-05-01

    Neutrophil-lymphocyte ratio (NLR) and BMI were examined as pre-operative predictors for lymph node metastases in patients with low-risk endometrial cancer. The study was a retrospective analysis of 534 endometrial cancer patients that underwent hysterectomy and lymph node dissection. Included subjects had a preoperative diagnosis of a grade 1 or 2 endometrioid carcinoma and no macroscopic extrauterine disease. We compared node-negative to node-positive patients to identify correlates of node-positive disease. The node-positive group presented with lower BMI than the node-negative group, 31.5 and 34.4, respectively (p = .03). The mean NLR was higher in the node-positive group 3.4 vs 2.9 (p = .08), showing a trend towards significance on univariate analysis. On multivariate analysis, lower BMI was found to be an independent predictor for nodal metastasis. Our data suggest that lower BMI is a risk factor for lymph nodes involvement in low-risk endometrial cancer. Impact statement Most endometrial cancer patients have low-risk disease with low risk for lymph nodes metastasis. In order to reduce the number of patients that will undergo unnecessary lymph node dissection, different types of preoperative predictors for lymph node involvement were studied. CA 125 and different imaging modalities were found as useful predictors for more advanced disease. Less studied predictors are the systemic inflammatory response markers and patient's BMI. This study suggests that lower BMI is a risk factor for lymph node involvement in low-risk endometrial cancer. The neutrophil to lymphocyte ratio was close to significance as a predictor for lymph node involvement. In practice, physicians might favour comprehensive lymph node dissection when there is a doubt regarding the procedure but the patient is lean. The study's conclusion can be utilised for triaging patients to general gynaecologist vs gynaecologic oncologist. Further research should focus on combining predictors such as

  15. Endometriosis and risks for ovarian, endometrial and breast cancers

    DEFF Research Database (Denmark)

    Mogensen, Julie Brøchner; Kjær, Susanne K.; Mellemkjær, Lene

    2016-01-01

    Objective A growing body of evidence suggests that endometriosis increases the risk for ovarian cancer, but it is less well studied whether the excess risk is confined to certain histotypes. Furthermore, it is not fully resolved if endometriosis is associated with endometrial- and breast cancer.......64; 95% CI: 2.36–5.38). An excess risk was also observed for endometrial cancer (SIR 1.43; 95% CI: 1.13–1.79), primarily of type 1 (SIR 1.54; 95% CI: 1.20–1.96); and the risk for breast cancer was increased among women aged ≥ 50 years at first diagnosis of endometriosis (SIR 1.27; 95% CI: 1.......12–1.42). Conclusions The results corroborate previous findings of increased risks for endometrioid and clear-cell ovarian cancer in women with endometriosis. As the first cohort study to date, we observed a significantly increased risk for endometrial cancer in women with a diagnosis of endometriosis. The increased...

  16. Consumption of sugary foods and drinks and risk of endometrial cancer.

    Science.gov (United States)

    King, Melony G; Chandran, Urmila; Olson, Sara H; Demissie, Kitaw; Lu, Shou-En; Parekh, Niyati; Bandera, Elisa V

    2013-07-01

    Consumption of foods high in sugar promotes insulin production, which has been linked to endometrial carcinogenesis. We evaluated the impact of dietary intake of sugary foods and beverages, as well as added sugar and total sugar on endometrial cancer risk in a population-based case-control study, including 424 cases and 398 controls. Participants completed an interview and food frequency questionnaire, and provided self-recorded waist and hip measurements. Women in the highest quartile of added sugar intake had significantly increased endometrial cancer risk (OR = 1.84, 95% CI 1.16-2.92). Among women with waist-to-hip ratio ≥0.85, risk was significantly higher for the highest versus lowest tertile of added sugar intakes (OR = 2.50, 95% CI 1.38-4.52). The association with added sugar also became stronger when analyses were restricted to never users of hormone replacement therapy (OR = 2.03; 95% CI 1.27-3.26, for highest versus lowest tertile). There was little evidence of effect modification by body mass index or physical activity. Given the high prevalence of intake of sugary foods and drinks in Western populations, additional research is warranted to confirm our findings on endometrial cancer.

  17. Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2)

    Science.gov (United States)

    Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A

    2015-01-01

    Background: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. Methods: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59–1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13–1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Conclusions: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters. PMID:25688738

  18. Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).

    Science.gov (United States)

    Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A

    2015-03-03

    Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

  19. Age at Last Birth in Relation to Risk of Endometrial Cancer: Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium

    Science.gov (United States)

    Setiawan, Veronica Wendy; Pike, Malcolm C.; Karageorgi, Stalo; Deming, Sandra L.; Anderson, Kristin; Bernstein, Leslie; Brinton, Louise A.; Cai, Hui; Cerhan, James R.; Cozen, Wendy; Chen, Chu; Doherty, Jennifer; Freudenheim, Jo L.; Goodman, Marc T.; Hankinson, Susan E.; Lacey, James V.; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Lurie, Galina; Mack, Thomas; Matsuno, Rayna K.; McCann, Susan; Moysich, Kirsten B.; Olson, Sara H.; Rastogi, Radhai; Rebbeck, Timothy R.; Risch, Harvey; Robien, Kim; Schairer, Catherine; Shu, Xiao-Ou; Spurdle, Amanda B.; Strom, Brian L.; Thompson, Pamela J.; Ursin, Giske; Webb, Penelope M.; Weiss, Noel S.; Wentzensen, Nicolas; Xiang, Yong-Bing; Yang, Hannah P.; Yu, Herbert; Horn-Ross, Pamela L.; De Vivo, Immaculata

    2012-01-01

    Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (Ptrend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. PMID:22831825

  20. Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study

    Science.gov (United States)

    Xu, Wang Hong; Zheng, Wei; Xiang, Yong Bing; Ruan, Zhi Xian; Cheng, Jia Rong; Dai, Qi; Gao, Yu Tang; Shu, Xiao Ou

    2004-01-01

    Objective To evaluate the association of intake of soya food, a rich source of phytoestrogens, with the risk of endometrial cancer. Design Population based case-control study, with detailed information on usual soya food intake over the past five years collected by face to face interview using a food frequency questionnaire. Setting Urban Shanghai, China. Participants 832 incident cases of endometrial cancer in women aged of 30 to 69 years diagnosed during 1997-2001 and identified from the Shanghai Cancer Registry; 846 control women frequency matched to cases on age and randomly selected from the Shanghai Residential Registry. Main outcome measures Odds ratios for risk of endometrial cancer in women with different intakes of soya foods. Results Regular consumption of soya foods, measured as amount of either soya protein or soya isoflavones, was inversely associated with the risk of endometrial cancer. Compared with women with the lowest quarter of intake, the adjusted odds ratio of endometrial cancer was reduced from 0.93 to 0.85 and 0.67 with increasing quarter of soya protein intake (P for trend 0.01). A similar inverse association was observed for soya isoflavones and soya fibre intake. The inverse association seemed to be more pronounced among women with high body mass index and waist:hip ratio. Conclusion Regular intake of soya foods is associated with a reduced risk of endometrial cancer. PMID:15136343

  1. Endometrial cancer

    Science.gov (United States)

    ... to your hormones increase your risk of endometrial cancer: Estrogen replacement therapy without the use of progesterone History of endometrial polyps Infrequent periods Never being pregnant Obesity Polycystic ovary syndrome (PCOS) Starting menstruation at an ...

  2. Body weight in early adulthood, adult weight gain, and risk of endometrial cancer in women not using postmenopausal hormones.

    Science.gov (United States)

    Stevens, Victoria L; Jacobs, Eric J; Patel, Alpa V; Sun, Juzhong; Gapstur, Susan M; McCullough, Marjorie L

    2014-03-01

    High body mass index (BMI) measured in middle age or later is an established risk factor for endometrial cancer. However, whether BMI measured in early adulthood and adult weight change are associated with endometrial cancer risk is less clear, particularly among nonusers of postmenopausal hormones (PMH). These associations were investigated among women in the Cancer Prevention Study II Nutrition Cohort. Women taking PMH (n = 11,624, 12 % of all women) were excluded, and the analysis was limited to 33,057 postmenopausal women who did not take PMH. Between enrollment in 1992/1993 and 30 June 2009, 447 women were diagnosed with endometrial cancer. Cox proportional hazards regression was used to calculate hazard rate ratios (RR) and corresponding 95 % confidence intervals (CI) for the association of BMI at age 18, calculated from recalled weight, and weight change between age 18 and 1992, with endometrial cancer incidence. BMI at age 18 was associated with higher risk of endometrial cancer in multivariable models adjusted for other risk factors (RR 1.29, 95 % CI 1.12-1.49 per 5 BMI units). Similarly, adult weight change was associated with higher risk of endometrial cancer (RR 1.81, 95 % CI 1.66-1.98 per 5 BMI unit change) in multivariable models adjusted for other risk factors. High BMI at age 18 and greater adult weight gain were strongly associated with risk of endometrial cancer. These results underscore the importance of both avoiding overweight/obesity in young adulthood and preventing weight gain thereafter to minimize risk of this cancer.

  3. Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study.

    Science.gov (United States)

    Budhathoki, S; Iwasaki, M; Sawada, N; Yamaji, T; Shimazu, T; Sasazuki, S; Inoue, M; Tsugane, S

    2015-02-01

    Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. Prospective cohort study. Ten public health centre areas in Japan. Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire. Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Incidence of endometrial cancer. During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk. © 2014 Royal College of Obstetricians and Gynaecologists.

  4. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer

    NARCIS (Netherlands)

    Bergman, L; Beelen, MLR; Gallee, MPW; Hollema, H; Benraadt, J; van Leeuwen, FE

    2000-01-01

    Background Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. Methods We did a nationwide case-control study on the risk

  5. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study

    National Research Council Canada - National Science Library

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-01-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS...

  6. Endometrial Cancer

    Science.gov (United States)

    ... healthy lifestyle is recommended after cancer treatment. Several studies have found that obesity, high blood pressure, and diabetes can contribute to long-term health risks for women with type 1 endometrial cancer. A healthy diet and regular exercise can help ...

  7. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

    DEFF Research Database (Denmark)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka

    2008-01-01

    Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention...... strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135...... persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers...

  8. Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

    Science.gov (United States)

    Bharati, Rajani; Jenkins, Mark A; Lindor, Noralane M; Le Marchand, Loïc; Gallinger, Steven; Haile, Robert W; Newcomb, Polly A; Hopper, John L; Win, Aung Ko

    2014-05-01

    To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer. We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer. A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83-1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75-4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63-5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Association of obesity-related genetic variants with endometrial cancer risk: a report from the Shanghai Endometrial Cancer Genetics Study.

    Science.gov (United States)

    Delahanty, Ryan J; Beeghly-Fadiel, Alicia; Xiang, Yong-Bing; Long, Jirong; Cai, Qiuyin; Wen, Wanqing; Xu, Wang-Hong; Cai, Hui; He, Jing; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao Ou

    2011-11-15

    Obesity is a well-established risk factor for endometrial cancer, the most common gynecologic malignancy. Recent genome-wide association studies (GWAS) have identified multiple genetic markers for obesity. The authors evaluated the association of obesity-related single nucleotide polymorphisms (SNPs) with endometrial cancer using GWAS data from their recently completed study, the Shanghai Endometrial Cancer Genetics Study, which comprised 832 endometrial cancer cases and 2,049 controls (1996-2005). Thirty-five SNPs previously associated with obesity or body mass index (BMI; weight (kg)/height (m)(2)) at a minimum significance level of ≤5 × 10(-7) in the US National Human Genome Research Institute's GWAS catalog (http://genome.gov/gwastudies) and representing 26 unique loci were evaluated by either direct genotyping or imputation. The authors found that for 22 of the 26 unique loci tested (84.6%), the BMI-associated risk variants were present at a higher frequency in cases than in population controls (P = 0.0003). Multiple regression analysis showed that 9 of 35 BMI-associated variants, representing 7 loci, were significantly associated (P ≤ 0.05) with the risk of endometrial cancer; for all but 1 SNP, the direction of association was consistent with that found for BMI. For consistent SNPs, the allelic odds ratios ranged from 1.15 to 1.29. These 7 loci are in the SEC16B/RASAL, TMEM18, MSRA, SOX6, MTCH2, FTO, and MC4R genes. The associations persisted after adjustment for BMI, suggesting that genetic markers of obesity provide value in addition to BMI in predicting endometrial cancer risk.

  10. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...

  11. Dietary total antioxidant capacity in relation to endometrial cancer risk: a case-control study in Italy.

    Science.gov (United States)

    Rossi, Marta; Tavani, Alessandra; Ciociola, Valentina; Ferraroni, Monica; Parpinel, Maria; Serafini, Mauro; Bellocco, Rino; Zucchetto, Antonella; Montella, Maurizio; Serraino, Diego; Lagiou, Pagona; La Vecchia, Carlo

    2016-03-01

    To investigate the role of the overall antioxidant activity of diet, we estimated the relation between three dietary indices of total antioxidant capacity (TAC) and endometrial cancer risk We analyzed data from an Italian case-control study including 454 women with incident, histologically confirmed endometrial cancer, and 908 frequency-matched controls admitted to the same hospitals as cases for acute non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' habitual diet. TAC was measured using Italian food composition tables in terms of Ferric-reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter (TRAP). We computed odds ratios (OR) and corresponding 95 % confidence intervals (CIs) using conditional multiple logistic regression models, including terms for recognized endometrial cancer risk factors and total energy intake. TAC was inversely related to endometrial cancer risk with ORs for the highest versus the lowest quartile of 0.69 (95 % CI 0.47-1.00) for FRAP, 0.68 (95 % CI 0.46-0.99) for TEAC, and 0.68 (95 % CI 0.47-0.98) for TRAP. The relations appeared consistent in strata of selected risk factors and decreased when considering TAC without the contribution of coffee. Our findings suggest a favorable role of a diet high in TAC on endometrial cancer risk, which can be partially driven by coffee consumption.

  12. Statin use and risk of endometrial cancer: a nationwide registry-based case-control study.

    Science.gov (United States)

    Sperling, Cecilie D; Verdoodt, Freija; Friis, Søren; Dehlendorff, Christian; Kjaer, Susanne K

    2017-02-01

    Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer. Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy (HRT), obesity, diabetes, chronic obstructive pulmonary disease and education. We evaluated whether the association between statin use and endometrial cancer varied with duration and intensity of statin use, type of endometrial cancer or patient characteristics. The study population comprised 5382 endometrial cancer cases and 72 127 population controls. We observed no association between ever use of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94-1.14). In addition, endometrial cancer risk did not vary substantially with duration or intensity of statin use. Stratification by type of endometrial cancer also yielded neutral ORs. In our nationwide case-control study, we found no association between statin use and risk of endometrial cancer. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  13. Variants in hormone biosynthesis genes and risk of endometrial cancer

    Science.gov (United States)

    Olson, Sara H.; Orlow, Irene; Bayuga, Sharon; Sima, Camelia; Bandera, Elisa V.; Pulick, Katherine; Faulkner, Shameka; Tommasi, Diana; Egan, Daniel; Roy, Pampa; Wilcox, Homer; Asya, Ali; Modica, Ippolito; Asad, Haider; Soslow, Robert; Zauber, Ann G.

    2009-01-01

    We investigated the risk associated with variants in three genes involved in estrogen biosynthesis, CYP11A1, CYP17A1, and CYP19A1, in the population-based case control study of Estrogen, Diet, Genetics, and Endometrial Cancer. This study was conducted in New Jersey in 2001–2006 with 417 cases and 402 controls. For CYP11A1, there was no association between the number of [TTTTA]n repeats (D15S520) and risk. For CYP17A1, risk was somewhat lower among women with the C/C genotype at T-34C (rs743572) (adjusted OR=0.65, 95% CI 0.41–1.02). For CYP19A1, risk was lower among women homozygous for the 3-base pair deletion (rs11575899) in exon 4 (adjusted OR=0.44, 95% CI 0.26–0.76), while the number of [TTTA]n repeats was not significantly related to risk: the adjusted OR for n=7/7 repeats vs n>7/>7 repeats was 0.81 (95% CI 0.54–1.23). In stratified analyses, results for CYP19A1 were stronger among women with higher (>27.4) body mass index: for the homozygous deletion, OR=0.30 (95% CI 0.15–0.62); for the n=7/7 genotype, OR=0.49 (95% CI 0.26–0.93). The interaction between the n=7/7 genotype and BMI was statistically significant (p=0.01). The insertion/deletion variant in CYP19A1 appears to be related to risk of endometrial cancer; risk associated with variants in this gene may vary according to BMI. PMID:18437511

  14. [Obesity, a main risk factor for endometrial cancer].

    Science.gov (United States)

    Ortiz-Mendoza, Carlos Manuel; Velasco-Navarro, Claudia

    2013-01-01

    obesity is a well-known risk factor for endometrial cancer, and both diseases are rising in Mexico. However, in our country some data indicates low influence of obesity on this neoplasm, and this is contradictory. Therefore, we explore the prevalence of obesity on women affected with this malignant tumor. this was a pilot case-control study in a general hospital at Mexico City. The analysis involved obesity (a body mass index ≥ 30 kg/m(2)) diabetes mellitus and systemic arterial hypertension. the sample was of 66 women: 22 cases and 44 controls. In cases, obesity occurred in 77 % (odds ratio [OR] 8.1, 95 % confidence interval [CI] 2.46-26.6); diabetes mellitus in 41 % (OR 4.3, CI 1.31-14.7); and systemic arterial hypertension in 41 % (OR 2.3, CI 0.78-7.1). these preliminary results suggested that obesity was the most frequent risk factor for these women with endometrial cancer.

  15. Lower mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of endometrial cancer.

    Science.gov (United States)

    Sun, Yuhui; Zhang, Liren; Ho, Simon S; Wu, Xifeng; Gu, Jian

    2016-06-01

    Mitochondria are the primary source of energy generation in human cells. Low mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) has been associated with obesity and increased risks of several cancers. Since obesity is a significant risk factor for endometrial cancer, we hypothesize that low mtDNA copy number in PBLs is associated with an increased susceptibility to endometrial cancer. Using a Caucasian case-control study, we measured mtDNA copy number in PBLs from 139 endometrial cancer patients and 139 age-matched controls and determined the association of mtDNA copy number with the risk of endometrial cancer using multivariate logistic regression analysis. The normalized mtDNA copy number was significantly lower in endometrial cancer cases (median, 0.84; range, 0.24-2.00) than in controls (median, 1.06; range, 0.64-1.96) (P endometrial cancer (adjusted OR, 5.59; 95%CI, 3.05-10.25; P obesity in elevating the risk of endometrial cancer. Low mtDNA copy number in PBLs is significantly associated with an increased risk of endometrial cancer in Caucasians. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  16. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

    DEFF Research Database (Denmark)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka

    2008-01-01

    Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention...... strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135...

  17. Preservation of the endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound ablation of submucosal uterine fibroids.

    Science.gov (United States)

    Kim, Young-Sun; Kim, Tae-Joong; Lim, Hyo Keun; Rhim, Hyunchul; Jung, Sin-Ho; Ahn, Joong Hyun; Lee, Jeong-Won; Kim, Byoung-Gie

    2017-09-01

    To evaluate the integrity of endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of submucosal uterine fibroids based on contrast-enhanced MRI findings, and to identify the risk factors for endometrial impairment. In total, 117 submucosal fibroids (diameter: 5.9 ± 3.0 cm) in 101 women (age: 43.6 ± 4.4 years) treated with MR-HIFU ablation were retrospectively analysed. Endometrial integrity was assessed with contrast-enhanced T1-weighted images at immediate (n = 101), 3-month (n = 62) and 12-month (n = 15) follow-ups. Endometrial impairment was classified into grades 0 (continuous endometrium), 1 (pin-point, full-thickness discontinuity), 2 (between grade 1 and 3), or 3 (full-thickness discontinuity >1 cm). Risk factors were assessed with generalized estimating equation (GEE) analysis. Among 117 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed at initial examination in 56.4%, 24.8%, 13.7% and 4.3%, respectively. Among 37 fibroid cases of endometrial impairment for which follow-ups were conducted, 30 showed improvements at 3- and/or 12-month follow-up. GEE analysis revealed the degree of endometrial protrusion was significantly associated with severity of endometrial injury (P HIFU ablation of submucosal fibroids, endometrial enhancement was preserved intact or minimally impaired in most cases. Impaired endometrium, which is more common after treating endometrially-protruded fibroids, may recover spontaneously. • After MR-HIFU ablation for submucosal fibroid, endometrium is mostly preserved/minimally impaired. • Endometrial-protruded submucosal fibroid is susceptible to more severe endometrial impairment. • The impaired endometrium may recover spontaneously at follow-up MR exams.

  18. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma

    NARCIS (Netherlands)

    Dove-Edwin, Isis; Boks, Dominique; Goff, Sheila; Kenter, Gemma G.; Carpenter, Robert; Vasen, Hans F. A.; Thomas, Huw J. W.

    2002-01-01

    BACKGROUND: Endometrial carcinoma is the most common extracolonic malignancy associated with hereditary nonpolyposis colorectal carcinoma syndrome (HNPCC). The risk of endometrial carcinoma in HNPCC mutation carriers is approximately ten times that of the general population, and endometrial

  19. Self-reported stress and risk of endometrial cancer: a prospective cohort study

    DEFF Research Database (Denmark)

    Nielsen, Naja Rod; Strandberg-Larsen, Katrine; Grønbaek, Morten

    2007-01-01

    -up, 72 women were diagnosed with endometrial cancer. For each increase in stress level on a 7-point stress scale, there was a lower risk of primary endometrial cancer (hazard ratio (HR) = 0.88; 95% confidence interval (CI), 0.76-1.01). This inverse association was particularly strong in women who...

  20. Risk of endometrial cancer in relationship to cigarette smoking : Results from the EPIC study

    NARCIS (Netherlands)

    AI-Zoughool, Mustafa; Dossus, Laure; Kaaks, Rudolf; Clavel-Chapelon, Francoise; Tjormeland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Gauthier, Estelle; Linseisen, Jakob; Chang-Claude, Jenny; Boeing, Heiner; Schulz, Mandy; Trichopoulou, Antonia; Chryssa, Travezea; Trichopoulos, Dimitrios; Berrino, Franco; Pallilo, Domenico; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H. Bas; Boshuizen, Hendrick C.; Peeters, Petra H. M.; Gram, Inger T.; Braaten, Tonje; Lund, Eiliv; Chirlaque, Maria-Dolores; Ardanaz, Eva; Agudo, Antonio; Larranaga, Nerea; Quiros, Jose Ramon; Berglund, Goran; Manjer, Jonas; Lundin, Eva; Halmans, Goran; Khaw, Kay-Tee; Bingham, Sheila; Allen, Naomi; Key, Tim; Jenab, Mazda; Cust, Anne E.; Rinaldi, Sabina; Riboli, Elio

    2007-01-01

    Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible

  1. Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative.

    Science.gov (United States)

    Reeves, Katherine W; Carter, Gebra Cuyun; Rodabough, Rebecca J; Lane, Dorothy; McNeeley, S Gene; Stefanick, Marcia L; Paskett, Electra D

    2011-05-01

    Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer. We studied 86937 postmenopausal women enrolled in the Women's Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade. During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade. Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Birth weight and the risk of histological subtypes of ovarian and endometrial cancers

    DEFF Research Database (Denmark)

    Trabert, Britton; Aarestrup, Julie; Ulrich, Lian G

    2018-01-01

    BACKGROUND: Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ova...

  3. Less favourable prognosis for low risk endometrial cancer patients with a discordant pre versus post operative risk stratification

    NARCIS (Netherlands)

    Eggink, F.a.; Mom, C.h.; Bouwman, K.; Boll, D.; Becker, J.h.; Creutzberg, C.l.; Niemeijer, G.c.; Van Driel, W.j.; Reyners, A.k.; Van Der Zee, A.g.; Bremer, G.l.; Ezendam, N.P.M.; Kruitwagen, R.f.; Pijnenborg, J.m.; Hollema, H.; Nijman, H.w.; Van Der Aa, M.a.

    2017-01-01

    Background: pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (ec). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival. Methods: patients diagnosed with ec

  4. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment.

    Science.gov (United States)

    Onstad, Michaela A; Schmandt, Rosemarie E; Lu, Karen H

    2016-12-10

    In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer.

  5. Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer

    DEFF Research Database (Denmark)

    Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    -matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting......PURPOSE: We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. METHODS: Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age...... for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated. RESULTS: We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated...

  6. Tubal Ligation and Risk of Endometrial Cancer: Findings From the Women's Health Initiative.

    Science.gov (United States)

    Winer, Ira; Lehman, Amy; Wactawski-Wende, Jean; Robinson, Randal; Simon, Michael; Cote, Michele

    2016-03-01

    Bilateral tubal ligation (BTL) is a common form of birth control in the United States. There are limited, contradictory data examining BTL and the risk of endometrial cancer and none examining type I and type II cancers separately. We investigated the association between BTL and endometrial cancer risk using the Women's Health Initiative (WHI) Observational and Dietary Modification Studies. Demographic information and history of BTL were obtained from the baseline questionnaires from 76,483 WHI participants in the Observational and Dietary Modification Studies. Univariable and multivariable models were used to examine the association of BTL with type I and type II endometrial cancers. A total of 1137 women were diagnosed with incident endometrial cancer (972 type I and 128 type II) during a mean follow-up of 11.3 years. Overall, 14,499 (19%) women had undergone BTL. There were no statistically significant associations noted between BTL and age at BTL for type I or type II cancers. We examined the largest patient cohort to date in an effort to determine the impact of BTL on endometrial cancer risk. In the WHI trial, we observed no overall effect of BTL on the risk of type I or type II endometrial cancer, suggesting that patients undergoing this popular birth control method likely do not have an associated change in their baseline risk for endometrial cancer.

  7. Genetic variations in UGT1A1 and UGT2B7 and endometrial cancer risk

    Science.gov (United States)

    McGrath, Monica; Lepine, Johanie; Lee, I-Min; Villeneuve, Lyne; Buring, Julie; Guillemette, Chantal; De Vivo, Immaculata

    2009-01-01

    UDP-glucuronosyltransferases (UGTs) are a family of phase II metabolizing enzymes involved in glucuronic acid conjugation of sex-steroid hormones. UGT1A1 and UGT2B7 are expressed in the uterus and involved in conjugation and elimination of estrogens. Chronic exposure to estrogens is associated with endometrial cancer. Functional polymorphisms have been identified in UGT1A1 and UGT2B7. We hypothesized that these variants may be associated with endometrial cancer risk. We conducted a case-control study nested within the Nurses’ Health Study and Women’s Health Study to investigate the associations between five polymorphisms and endometrial cancer risk using 593 invasive endometrial cancer cases and 1,545 controls. We did observe the suggestion of an inverse association with homozygote variant carriers of UGT1A1*28 and endometrial cancer risk. We did not observe significant associations between individual SNPs and UGT1A1 haplotypes and endometrial cancer risk. Our data suggests that these UGT polymorphisms do not contribute significantly to endometrial cancer risk. PMID:19352303

  8. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    Directory of Open Access Journals (Sweden)

    Concetta Laliscia

    2016-12-01

    Full Text Available Purpose : The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR vaginal brachytherapy (BT. Material and methods : Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week. Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results : According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9% and in stage IB (57.9%. Thirty-three patients (26.2% received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS and five-year overall survival (OS were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3% and dyspareunia (7 patients, 5.5%. Two patients (1.6% had more than one toxicity. Late toxicity occurred in 20 patients (15.9%. Grade 1-2 late toxicities were fibrosis (14 patients, 11.1% and telangiectasias (7 patients, 5.5%. Six patients (4.8% had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions : These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.

  9. An Aggregated Analysis of Hormonal Factors and Endometrial Cancer Risk by Parity

    Science.gov (United States)

    Schonfeld, Sara J.; Hartge, Patricia; Pfeiffer, Ruth M.; Freedman, D. Michal; Greenlee, Robert T.; Linet, Martha S.; Park, Yikyung; Schairer, Catherine; Visvanathan, Kala; Lacey, JV

    2013-01-01

    Background Nulliparity is associated with an increased risk of endometrial cancer. Less clear is whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies are too small to test the hypothesis that endometrial cancer risk factors may be more strongly associated with risk among nulliparous women compared with parous women. Methods We aggregated data on 26,936 postmenopausal, Caucasian nulliparous women (360 endometrial cancers) and 146,583 postmenopausal Caucasian parous women (1,378 endometrial cancers) from four U.S. prospective studies (1979–2006). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) in stratified analyses. Results As expected, endometrial cancer risk was higher among nulliparous women than among parous women (HR, nulliparous vs. parous = 1.42, 95% CI 1.26 to 1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ among nulliparous vs. parous women: among both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity; body mass index ≥30 kg/m2 (vs. endometrial cancer risk three-fold among nulliparous (HR= 3.04, 95% CI 2.34 to 3.94) and parous (HR= 2.88, 95% CI 2.52 to 3.29) women. Conclusions The results from this large, pooled analysis of data from four large prospective studies suggest that nulliparity does not modify endometrial cancer risks associated with established hormone-related risk factors. PMID:23280123

  10. High rates of endometrial cancer among Pacific women in New Zealand: the role of diabetes, physical inactivity, and obesity.

    Science.gov (United States)

    Meredith, Ineke; Sarfati, Diana; Ikeda, Takayoshi; Atkinson, June; Blakely, Tony

    2012-06-01

    To determine the endometrial cancer rates, and the proportion attributable to diabetes mellitus (DM), physical inactivity, and overweight/obesity, by ethnicity with a focus on Pacific women in New Zealand. Linked census-cancer records (1981-2004) were used to determine incidence rates of endometrial cancer by ethnicity. Health survey data (2006-2007) were used to determine risk factor prevalence by ethnicity. Relative risks for the association between diabetes, obesity, physical inactivity and endometrial cancer were sourced from published studies. Population attributable risk (PAR) methods, with Monte Carlo simulation, were used to estimate the PAR% by ethnicity and applied to 2001-2004 cancer rates. Pacific women had 2.61 (95 % confidence interval 2.22-3.05) times the endometrial cancer rate of European/Other women pooled over time, and the most rapidly increasing rates over time with the rate ratio increasing from 1.96 (1.14-3.37) in 1981/1986 to 3.78 (3.03-4.71) in 2001/2004 (p for trend = 0.14). Pacific women had the highest PAR% for DM, physical inactivity, and overweight/obesity (63.1 %), followed by Māori (58.6 %) and European/Other (48.6 %). Applying these PAR% to 2001-2004 endometrial cancer rates, the rate ratio comparing Pacific to European/Other endometrial cancer reduced from 3.8 for total cancer (attributable plus non-attributable) to 2.3 for non-attributable cancer, and the rate difference reduced by 79 % from 51 to 11 per 100,000. Pacific women have high endometrial cancer rates in New Zealand. Some, but not all, of the ethnic inequalities were explained by measured differences in obesity/overweight, DM, and physical inactivity.

  11. Simultaneous Integrated Boost Volumetric Modulated Arc Therapy in the Postoperative Treatment of High-Risk to Intermediate-Risk Endometrial Cancer: Results of ADA II Phase 1-2 Trial.

    Science.gov (United States)

    Macchia, Gabriella; Cilla, Savino; Deodato, Francesco; Ianiro, Anna; Legge, Francesco; Marucci, Martina; Cammelli, Silvia; Perrone, Anna Myriam; De Iaco, Pierandrea; Gambacorta, Maria Antonietta; Autorino, Rosa; Valentini, Vincenzo; Morganti, Alessio G; Ferrandina, Gabriella

    2016-11-01

    A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort received higher doses (60 Gy in 2.4-Gy fractions). Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity-free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). This clinical study showed the feasibility of this technique and its good profile in terms of acute and

  12. Simultaneous Integrated Boost Volumetric Modulated Arc Therapy in the Postoperative Treatment of High-Risk to Intermediate-Risk Endometrial Cancer: Results of ADA II Phase 1-2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso (Italy); Cilla, Savino [Medical Physics Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso (Italy); Deodato, Francesco [Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso (Italy); Ianiro, Anna [Medical Physics Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso (Italy); Legge, Francesco [Gynecologic Oncology Unit, F. Miulli General Regional Hospital, Acquaviva delle Fonti, Bari (Italy); Marucci, Martina [Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso (Italy); Cammelli, Silvia [Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna (Italy); Perrone, Anna Myriam; De Iaco, Pierandrea [Gynecologic Oncology Unit, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna (Italy); Gambacorta, Maria Antonietta; Autorino, Rosa [Department of Radiotherapy, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome (Italy); Valentini, Vincenzo [Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso (Italy); Department of Radiotherapy, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome (Italy); and others

    2016-11-01

    Purpose: A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. Methods and Materials: Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort received higher doses (60 Gy in 2.4-Gy fractions). Results: Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity–free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). Conclusions: This clinical study showed the feasibility of this

  13. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial.

    Science.gov (United States)

    de Boer, Stephanie M; Powell, Melanie E; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B; Ledermann, Jonathan A; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Kitchener, Henry C; Nijman, Hans W; Kruitwagen, Roy F; Nout, Remi A; Verhoeven-Adema, Karen W; Smit, Vincent T; Putter, Hein; Creutzberg, Carien L

    2016-08-01

    About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48·6 Gy) in 1·8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for

  14. An aggregated analysis of hormonal factors and endometrial cancer risk by parity.

    Science.gov (United States)

    Schonfeld, Sara J; Hartge, Patricia; Pfeiffer, Ruth M; Freedman, D Michal; Greenlee, Robert T; Linet, Martha S; Park, Yikyung; Schairer, Catherine; Visvanathan, Kala; Lacey, James V

    2013-04-01

    Nulliparity is associated with an increased risk of endometrial cancer. It is less clear whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies to date have been too small to test the hypothesis that endometrial cancer risk factors may be associated more strongly with risk among nulliparous women compared with parous women. Data were aggregated on 26,936 postmenopausal, Caucasian, nulliparous women (360 endometrial cancers) and 146,583 postmenopausal, Caucasian, parous women (1378 endometrial cancers) from 4 US prospective studies (1979-2006). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in stratified analyses. The risk of endometrial cancer was higher among nulliparous women than among parous women, as expected (nulliparous vs parous: HR, 1.42; 95% CI, 1.26-1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ between nulliparous versus parous women: For both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity: A body mass index ≥30 kg/m(2) (vs endometrial cancer 3-fold among nulliparous women (HR, 3.04; 95% CI, 2.34-3.94) and parous women (HR, 2.88; 95% CI, 2.52-3.29). The results from this large, pooled analysis of data from 4 large prospective studies suggested that nulliparity does not modify the risks of endometrial cancer associated with established hormone-related risk factors. Copyright © 2012 American Cancer Society.

  15. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility.

    Science.gov (United States)

    Skalkidou, Alkistis; Sergentanis, Theodoros N; Gialamas, Spyros P; Georgakis, Marios K; Psaltopoulou, Theodora; Trivella, Marialena; Siristatidis, Charalampos S; Evangelou, Evangelos; Petridou, Eleni

    2017-03-25

    with an increased risk of endometrial cancer (RR 0.96, 95% CI 0.67 to 1.37; 156,774 participants; very low quality evidence). Fifteen eligible studies, using a general population as the control group, found an increased risk after exposure to any ovary-stimulating drug (RR 1.75, 95% CI 1.18 to 2.61; 1,762,829 participants; very low quality evidence).Five eligible studies, confined to subfertile women (92,849 participants), reported on exposure to clomiphene citrate; the pooled studies indicated a positive association ( RR 1.32; 95% CI 1.01 to 1.71; 88,618 participants; very low quality evidence), although only at high dosage (RR 1.69, 95% CI 1.07 to 2.68; two studies; 12,073 participants) and at a high number of cycles (RR 1.69, 95% CI 1.16 to 2.47; three studies; 13,757 participants). Four studies found an increased risk of endometrial cancer in subfertile women who required clomiphene citrate compared to a general population control group (RR 1.87, 95% CI 1.00 to 3.48; four studies, 19,614 participants; very low quality evidence). These data do not tell us whether the association is due to the underlying conditions requiring clomiphene or the treatment itself.Using unexposed subfertile women as controls, exposure to gonadotropins was associated with an increased risk of endometrial cancer (RR 1.55, 95% CI 1.03 to 2.34; four studies; 17,769 participants; very low quality evidence). The respective analysis of two studies (1595 participants) versus the general population found no difference in risk (RR 2.12, 95% CI 0.79 to 5.64: very low quality evidence).Exposure to a combination of clomiphene citrate and gonadotropins, compared to unexposed subfertile women, produced no difference in risk of endometrial cancer (RR 1.18, 95% CI 0.57 to 2.44; two studies; 6345 participants; very low quality evidence). However, when compared to the general population, an increased risk was found , suggesting that the key factor might be subfertility, rather than treatment (RR 2.99, 95

  16. Preservation of the endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound ablation of submucosal uterine fibroids

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-sun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Uterine Fibroid Integrated Management Center, MINT Intervention Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Lim, Hyo Keun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); SAIHST, Sungkyunkwan University, Department of Health Sciences and Technology, Seoul (Korea, Republic of); Rhim, Hyunchul [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Jung, Sin-Ho [SAIHST, Sungkyunkwan University, Department of Health Sciences and Technology, Seoul (Korea, Republic of); Samsung Medical Center, Department of Biostatistics and Clinical Epidemiology, Seoul (Korea, Republic of); Ahn, Joong Hyun [Samsung Biomedical Research Institute, Samsung Medical Center, Biostatistics Team, Seoul (Korea, Republic of)

    2017-09-15

    To evaluate the integrity of endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of submucosal uterine fibroids based on contrast-enhanced MRI findings, and to identify the risk factors for endometrial impairment. In total, 117 submucosal fibroids (diameter: 5.9 ± 3.0 cm) in 101 women (age: 43.6 ± 4.4 years) treated with MR-HIFU ablation were retrospectively analysed. Endometrial integrity was assessed with contrast-enhanced T1-weighted images at immediate (n = 101), 3-month (n = 62) and 12-month (n = 15) follow-ups. Endometrial impairment was classified into grades 0 (continuous endometrium), 1 (pin-point, full-thickness discontinuity), 2 (between grade 1 and 3), or 3 (full-thickness discontinuity >1 cm). Risk factors were assessed with generalized estimating equation (GEE) analysis. Among 117 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed at initial examination in 56.4%, 24.8%, 13.7% and 4.3%, respectively. Among 37 fibroid cases of endometrial impairment for which follow-ups were conducted, 30 showed improvements at 3- and/or 12-month follow-up. GEE analysis revealed the degree of endometrial protrusion was significantly associated with severity of endometrial injury (P < 0.0001). After MR-HIFU ablation of submucosal fibroids, endometrial enhancement was preserved intact or minimally impaired in most cases. Impaired endometrium, which is more common after treating endometrially-protruded fibroids, may recover spontaneously. (orig.)

  17. Age dependent association of endometrial polyps with increased risk of cancer involvement

    Directory of Open Access Journals (Sweden)

    Martel Maritza

    2005-02-01

    Full Text Available Abstract Background Endometrial polyps (EMPs are commonly encountered in routine surgical pathology practice, but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. The objectives of the present study are 1 to investigate the age-group in which EMP are most commonly encountered 2 to document the age-group in which EMP are most commonly associated with malignancies 3 To investigate whether the age of diagnosis of the various carcinoma subtypes in EMPs is congruent with published data on similar malignancies arising in non-polypoid endometrium and 4 To investigate whether the histologic subtype distribution of malignancies associated with EMPs are similar or different from the distribution of malignancies arising from non-polypoid endometrium based on published data. Patients and methods All cases of EMPs were retrieved from the files of Yale-New Haven Hospital for the period 1986–1995. The patients were divided into 5 age groups: Each group was further subclassified based on an association (or lack thereof of EMPs with endometrial carcinoma. Chi-square test was used to compare the proportion of malignancy associated EMPs between the age groups. Results We identified 513 EMPs, of which 209 (41% were from biopsy specimens and 304 (59% from hysterectomy specimens. Sixty six (13% of all EMPs were malignant. The 66 malignant EMPs included 58 endometrioid, 6 serous, 1 carcinosarcoma, and 1 clear cell carcinoma. In age group >35, only 1(2.5% of 40 EMPs was associated with endometrial malignancy. In contrast, 37(32% of 115 EMPs were associated with malignancy in the age group > 65. The frequency of malignant EMPs increased with age and reached statistical significance in the age group >65 (p Conclusions EMPs show statistically significant age dependent association with malignant tumor involvement. Careful search for malignancy, particularly in women with multiple risk factors is advised in daily practice

  18. Childhood BMI growth trajectories and endometrial cancer risk

    DEFF Research Database (Denmark)

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate

    2017-01-01

    Previously, we found that excess weight already in childhood has positive associations with endometrial cancer, however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial......, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain...... in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z-score increase were 1.15 (95...

  19. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lianlian Wang

    2015-07-01

    Full Text Available Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR: 0.77, 95% CI: 0.62–0.96, I2: 63.0%, especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95. A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99. Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk.

  20. Almost half of women with endometrial cancer or hyperplasia do not know that obesity affects their cancer risk

    OpenAIRE

    Beavis, Anna L.; Cheema, Simrin; Christine H. Holschneider; Erin L. Duffy; Amneus, Malaika W.

    2015-01-01

    Highlights • A group of low income, largely Hispanic women demonstrated poor knowledge of the adverse reproductive effects of obesity. • 53.5% of endometrial cancer/hyperplasia patients identified obesity as a risk factor for endometrial cancer. • 32% of control patients identified obesity as a risk factor for endometrial cancer. • Physician discussion of overweight/obese diagnosis was predictive of this knowledge.

  1. Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study.

    Science.gov (United States)

    Dossus, Laure; Rinaldi, Sabina; Becker, Susen; Lukanova, Annekatrin; Tjonneland, Anne; Olsen, Anja; Stegger, Jakob; Overvad, Kim; Chabbert-Buffet, Nathalie; Jimenez-Corona, Aida; Clavel-Chapelon, Francoise; Rohrmann, Sabine; Teucher, Birgit; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Palli, Domenico; Berrino, Franco; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Redondo, Maria-Luisa; Travier, Noémie; Sanchez, Maria-Jose; Altzibar, Jone M; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H Bas; van Duijnhoven, Fränzel J B; Onland-Moret, N Charlotte; Peeters, Petra H M; Hallmans, Goran; Lundin, Eva; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi; Key, Tim J; Slimani, Nadia; Hainaut, Pierre; Romaguera, Dora; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2010-12-01

    Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.

  2. Obesity, inflammatory markers, and endometrial cancer risk: a prospective case–control study

    Science.gov (United States)

    Dossus, Laure; Rinaldi, Sabina; Becker, Susen; Lukanova, Annekatrin; Tjonneland, Anne; Olsen, Anja; Stegger, Jakob; Overvad, Kim; Chabbert-Buffet, Nathalie; Jimenez-Corona, Aida; Clavel-Chapelon, Francoise; Rohrmann, Sabine; Teucher, Birgit; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Palli, Domenico; Berrino, Franco; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Redondo, Maria-Luisa; Travier, Noémie; Sanchez, Maria-Jose; Altzibar, Jone M; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H Bas; van Duijnhoven, Fränzel J B; Onland-Moret, N Charlotte; Peeters, Petra H M; Hallmans, Goran; Lundin, Eva; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi; Key, Tim J; Slimani, Nadia; Hainaut, Pierre; Romaguera, Dora; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2010-01-01

    Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03–2.41, Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu. PMID:20843938

  3. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E. A. E. M.; Ezendam, N. P. M.; Pijnenborg, J. M. A.

    2015-01-01

    Background Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  4. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E.A.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2015-01-01

    BACKGROUND: Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  5. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome.

    Science.gov (United States)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka; Bernstein, Inge; Aarnio, Markku; Järvinen, Heikki J; Myrhøj, Torben; Sunde, Lone; Wijnen, Juul T; Lynch, Henry T

    2008-07-15

    Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6-10.8); risks were higher in males (p < 0.02) and members of MSH2 families (p < 0.0001). Ovarian cancer (N = 72) had an lifetime risk of 6.7% (95% CI: 5.3-9.1); risks were higher in women born after the median year of birth (p < 0.008) and in members of MSH2 families (p < 0.006). Brain tumors and cancers of the small bowel, stomach, breast and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions. (c) 2008 Wiley-Liss, Inc.

  6. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.

    Directory of Open Access Journals (Sweden)

    Galina Lurie

    Full Text Available Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2. This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively. In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR  = 1.17; 95% confidence interval (CI: 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI, suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68. FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

  7. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.

    Science.gov (United States)

    Lurie, Galina; Gaudet, Mia M; Spurdle, Amanda B; Carney, Michael E; Wilkens, Lynne R; Yang, Hannah P; Weiss, Noel S; Webb, Penelope M; Thompson, Pamela J; Terada, Keith; Setiawan, Veronica Wendy; Rebbeck, Timothy R; Prescott, Jennifer; Orlow, Irene; O'Mara, Tracy; Olson, Sara H; Narod, Steven A; Matsuno, Rayna K; Lissowska, Jolanta; Liang, Xiaolin; Levine, Douglas A; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E; Garcia-Closas, Montserrat; Doherty, Jennifer Anne; De Vivo, Immaculata; Chen, Chu; Brinton, Louise A; Akbari, Mohammad R; Goodman, Marc T

    2011-02-08

    Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

  8. Endometrial Cancer Prevention

    Science.gov (United States)

    ... following protective factors decrease the risk of endometrial cancer: Pregnancy and breast-feeding Estrogen levels are lower during pregnancy and when breast-feeding. The risk of endometrial cancer is lower in women who have had children. ...

  9. Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer.

    Science.gov (United States)

    Nagle, C M; Marquart, L; Bain, C J; O'Brien, S; Lahmann, P H; Quinn, M; Oehler, M K; Obermair, A; Spurdle, A B; Webb, P M

    2013-08-01

    Obesity is an established risk factor for endometrial cancer. Associations tend to be stronger for the endometrioid subtype. The role of adult weight change and weight cycling is uncertain. Our study aimed to determine whether there is an association between different adult weight trajectories, weight cycling and risk of endometrial cancer overall, and by subtype. We analysed data from the Australian National Endometrial Cancer study, a population-based case-control study that collected self-reported information on height, weight at three time points (age 20, maximum and 1 year prior to diagnosis [recent]), intentional weight loss/regain (weight cycling) from 1398 women with endometrial cancer and 1538 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. Relative to women who maintained a stable weight during adulthood, greater weight gain after the age of 20 was associated with increased risk of endometrial cancer (OR for gain 40+kg all subtypes 5.3, 95% CI 3.9-7.3; endometrioid 6.5, 95% CI 4.7-9.0). The strongest associations were observed among women who were continually overweight from the age of 20 (all subtypes OR 3.6, 95% CI 2.6-5.0). Weight cycling was associated with increased risk, particularly among women who had ever been obese (OR 2.9 95% CI 1.8-4.7), with ~3-fold risks seen for both endometrioid and non-endometrioid tumour subtypes. Women who had intentionally lost weight and maintained that weight loss were not at increased risk. These results suggest that higher adult weight gain, and perhaps weight cycling, independently increase the risk of endometrial cancer, however women who lost weight and kept that weight off were not at increased risk. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Endometrial ablation

    Science.gov (United States)

    Hysteroscopy - endometrial ablation; Laser thermal ablation; Endometrial ablation - radiofrequency; Endometrial ablation - thermal balloon ablation; Rollerball ablation; Hydrothermal ablation; Novasure ...

  11. Endometrial biopsy

    Science.gov (United States)

    Biopsy - endometrium ... The biopsy is normal if the cells in the sample are not abnormal. ... Risks of endometrial biopsy include: Infection Causing a hole in (perforating) the uterus or tearing the cervix (rarely occurs) Prolonged bleeding Slight spotting ...

  12. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study.

    Science.gov (United States)

    Kempers, Marlies J E; Kuiper, Roland P; Ockeloen, Charlotte W; Chappuis, Pierre O; Hutter, Pierre; Rahner, Nils; Schackert, Hans K; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Büttner, Reinhard; Verwiel, Eugene T P; van Krieken, J Han; Nagtegaal, Iris D; Goossens, Monique; van der Post, Rachel S; Niessen, Renée C; Sijmons, Rolf H; Kluijt, Irma; Hogervorst, Frans B L; Leter, Edward M; Gille, Johan J P; Aalfs, Cora M; Redeker, Egbert J W; Hes, Frederik J; Tops, Carli M J; van Nesselrooij, Bernadette P M; van Gijn, Marielle E; Gómez García, Encarna B; Eccles, Diana M; Bunyan, David J; Syngal, Sapna; Stoffel, Elena M; Culver, Julie O; Palomares, Melanie R; Graham, Tracy; Velsher, Lea; Papp, Janos; Oláh, Edith; Chan, Tsun L; Leung, Suet Y; van Kessel, Ad Geurts; Kiemeney, Lambertus A L M; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J L

    2011-01-01

    Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions. We obtained clinical data for 194 carriers of a 3' end EPCAM deletion from 41 families known to us at the Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands and compared cancer risk with data from a previously described cohort of 473 carriers from 91 families with mutations in MLH1, MSH2, MSH6, or a combined EPCAM-MSH2 deletion. 93 of the 194 EPCAM deletion carriers were diagnosed with colorectal cancer; three of the 92 women with EPCAM deletions were diagnosed with endometrial cancer. Carriers of an EPCAM deletion had a 75% (95% CI 65-85) cumulative risk of colorectal cancer before the age of 70 years (mean age at diagnosis 43 years [SD 12]), which did not differ significantly from that of carriers of combined EPCAM-MSH2 deletion (69% [95% CI 47-91], p=0·8609) or mutations in MSH2 (77% [64-90], p=0·5892) or MLH1 (79% [68-90], p=0·5492), but was higher than noted for carriers of MSH6 mutation (50% [38-62], p<0·0001). By contrast, women with EPCAM deletions had a 12% [0-27] cumulative risk of endometrial cancer, which was lower than was that noted for carriers of a combined EPCAM-MSH2 deletion (55% [20-90], p<0·0001) or of a mutation in MSH2 (51% [33-69], p=0·0006) or MSH6 (34% [20-48], p=0·0309), but did not differ significantly from that noted for MLH1 (33% [15-51], p=0·1193) mutation carriers. This risk seems to be restricted to deletions that extend close to the MSH2 gene promoter. Of 194 carriers of an EPCAM deletion, three had duodenal cancer and four had pancreatic cancer. EPCAM deletion carriers have

  13. Anthropometry, physical activity, and endometrial cancer risk: Results from the Netherlands Cohort Study

    NARCIS (Netherlands)

    Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2004-01-01

    Although obesity is an established risk factor for endometrial cancer, evidence linking risk to height, weight change since age 20, and physical activity is limited. In this case-cohort study, 62 573 women from The Netherlands Cohort Study on Diet and Cancer were followed up from 1986 to 1995, and

  14. Risk of endometrial cancer in relation to medical conditions and medication use

    Science.gov (United States)

    Fortuny, Joan; Sima, Camelia; Bayuga, Sharon; Wilcox, Homer; Pulick, Katherine; Faulkner, Shameka; Zauber, Ann G.; Olson, Sara H.

    2009-01-01

    We studied the relation of medical conditions related to obesity and medications used for these conditions with endometrial cancer. We also investigated the association of other medical conditions and medications with risk. This US population-based case-control study included 469 endometrial cancer cases and 467 controls. Information on putative risk factors for endometrial cancer was collected through personal interviews. We asked women about their medical history and medications used for six months or longer and the number of years each medication was taken. Risk was strongly associated with increasing obesity (p for trend <0.001). Among conditions related to obesity, and after adjustment for age, body mass index (BMI), and other risk factors and conditions, uterine fibroids were independently related to an increased cancer risk (adjusted OR= 1.8, 95%CI= 1.2–2.5). Although hypertension was not significantly related to endometrial cancer after adjustment for age and BMI, use of thiazide diuretics was independently associated with an increased risk (OR= 1.8, 95%CI= 1.1–3.0). Anemia was associated with decreased risk (OR= 0.6, 95%CI= 0.5–0.9). Use of non-steroidal anti-inflammatory drugs was related to a decreased risk (OR= 0.7, 95%CI= 0.5–0.97). To our knowledge, the observation about thiazide diuretics is novel and requires confirmation in other studies and populations. PMID:19383893

  15. Risk of second primary cancers in women diagnosed with endometrial cancer in German and Swedish cancer registries.

    Science.gov (United States)

    Chen, Tianhui; Brenner, Hermann; Fallah, Mahdi; Jansen, Lina; Castro, Felipe A; Geiss, Karla; Holleczek, Bernd; Katalinic, Alexander; Luttmann, Sabine; Sundquist, Kristina; Ressing, Meike; Xu, Leiting; Hemminki, Kari

    2017-12-01

    Along with the increasing incidence and favorable prognosis, more women diagnosed with endometrial cancer may develop second primary cancers (SPCs). We aimed at investigating risk of SPCs after endometrial cancer in Germany and Sweden to provide insight into prevention strategies for SPCs. Endometrial cancer patients diagnosed at age ≥15 years in Germany during 1997-2011 and in Sweden nationwide during 1997-2012 were selected. Standardized incidence ratios (SIRs), calculated as the ratio of observed to expected numbers of cases, were used to assess the risk of a specific second cancer after endometrial cancer for both German and Swedish datasets. Among 46,929 endometrial cancer survivors in Germany and 18,646 in Sweden, overall 2,897 and 1,706 SPCs were recorded, respectively. Significantly elevated SIRs were observed in Germany for ovarian (SIR = 1.3; 95%CI:1.1-1.5) and kidney cancers [1.6 (1.3-1.8)], while in Sweden the SIRs were 5.4 (4.6-6.3) and1.4 (1.0-1.9), respectively. Elevated risk for second ovarian endometrioid carcinoma was pronounced after early (endometrial cancer in Germany [9.0 (4.8-15)] and Sweden [7.7 (5.1-11)]. In Germany elevated risks were found for second ovarian endometrioid carcinoma after endometrioid histology of first endometrial cancer [6.3 (4.0-9.4)] and for second kidney cancer after clear cell histology of endometrial cancer [4.9 (1.6-11)]. We found exceptionally elevated risk of second ovarian endometrioid carcinoma after endometrial cancer of the same histology or of early onset. Risk for second kidney cancer was also increased, particularly after endometrial cancer of clear cell histology. Cancer prevention strategies should focus on these cancers after endometrial cancer diagnosis. © 2017 UICC.

  16. Case-control study of lifetime alcohol consumption and endometrial cancer risk.

    Science.gov (United States)

    Friedenreich, Christine M; Speidel, Thomas P; Neilson, Heather K; Langley, Annie R; Courneya, Kerry S; Magliocco, Anthony M; Cook, Linda S

    2013-11-01

    Alcohol consumption is hypothesized to increase the risk of endometrial cancer by increasing circulating estrogen levels. This study sought to investigate the association between lifetime alcohol consumption and endometrial cancer risk. We recruited 514 incident endometrial cancer cases and 962 frequency age-matched controls in this population-based case-control study in Alberta, Canada, from 2002 to 2006. Participants completed in-person interviews querying lifetime alcohol consumption and other relevant health and lifestyle factors. Participants reported the usual number of drinks of beer, wine, and liquor consumed; this information was compiled for each drinking pattern reported over the lifetime to estimate average lifetime exposure to alcohol. Lifetime average alcohol consumption was relatively low (median intake: 3.9 g/day for cases, 4.9 g/day for controls). Compared with lifetime abstainers, women consuming >2.68 and ≤8.04 g/day alcohol and >8.04 g/day alcohol on average over the lifetime showed 38 and 35 % lower risks of endometrial cancer, respectively (p trend = 0.023). In addition, average lifetime consumption of all types of alcohol was associated with decreased risks. There was no evidence for effect modification by body mass index, physical activity, menopausal status, and hormone replacement therapy use combined and effects did not differ by type of endometrial cancer (type I or II). This study provides epidemiologic evidence for an inverse association between relatively modest lifetime average alcohol consumption (approximately 1/4 to 1/2 drink/day) and endometrial cancer risk. The direction of this relation is consistent with previous studies that examined similar levels of alcohol intake.

  17. Genetic variants in MUTYH are not associated with endometrial cancer risk.

    Science.gov (United States)

    Ashton, Katie A; Proietto, Anthony; Otton, Geoffrey; Symonds, Ian; Scott, Rodney J

    2009-01-26

    Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant inherited predisposition to a number of epithelial cancers, most notably colorectal and endometrial cancer. Outside of the context of Lynch syndrome there is little evidence for an autosomal dominant or recessive condition that predisposes to endometrial cancer. Recently, genetic variants in MUTYH have been associated with a recessive form of colorectal cancer, known as MUTYH associated polyposis or MAP. MUTYH is involved in base excision repair of DNA lesions and as such a breakdown in the fidelity of this process would necessarily not be predicted to result in a specific disease. At present there is little information about the role of MUTYH in other types of cancer and only one report indicating a possible relationship with endometrial cancer.Similar to a previous study, we investigated a series of endometrial cancer patients to determine if MUTYH variants were over-represented compared to a series of healthy control subjects and to assess whether or not endometrial cancer risk could be explained by an autosomal recessive model of inheritance.Two MUTYH mutations, Y165C and G382D, and three common MUTYH polymorphisms, V22M, Q324H and S501F, were genotyped in 213 endometrial cancer patients and 226 controls from Australia using real time PCR. Differences in genotype frequencies were compared using Chi-squared analysis and by calculating odds ratios and 95% confidence intervals.Three endometrial cancer patients were identified with heterozygous MUTYH mutations (two G382D and one Y165C). No bi-allelic mutation carriers were identified. Two of the three patients' clinical characteristics were similar to those commonly identified in HNPCC and lend support to the notion that MUTYH mutations increase the risk of developing HNPCC related diseases. There was no difference in the five genotype frequencies of the endometrial cancer patients compared to the controls

  18. Genetic variants in MUTYH are not associated with endometrial cancer risk

    Directory of Open Access Journals (Sweden)

    Ashton Katie A

    2009-01-01

    Full Text Available Abstract Hereditary non-polyposis colorectal cancer (HNPCC, also known as Lynch syndrome, is an autosomal dominant inherited predisposition to a number of epithelial cancers, most notably colorectal and endometrial cancer. Outside of the context of Lynch syndrome there is little evidence for an autosomal dominant or recessive condition that predisposes to endometrial cancer. Recently, genetic variants in MUTYH have been associated with a recessive form of colorectal cancer, known as MUTYH associated polyposis or MAP. MUTYH is involved in base excision repair of DNA lesions and as such a breakdown in the fidelity of this process would necessarily not be predicted to result in a specific disease. At present there is little information about the role of MUTYH in other types of cancer and only one report indicating a possible relationship with endometrial cancer. Similar to a previous study, we investigated a series of endometrial cancer patients to determine if MUTYH variants were over-represented compared to a series of healthy control subjects and to assess whether or not endometrial cancer risk could be explained by an autosomal recessive model of inheritance. Two MUTYH mutations, Y165C and G382D, and three common MUTYH polymorphisms, V22M, Q324H and S501F, were genotyped in 213 endometrial cancer patients and 226 controls from Australia using real time PCR. Differences in genotype frequencies were compared using Chi-squared analysis and by calculating odds ratios and 95% confidence intervals. Three endometrial cancer patients were identified with heterozygous MUTYH mutations (two G382D and one Y165C. No bi-allelic mutation carriers were identified. Two of the three patients' clinical characteristics were similar to those commonly identified in HNPCC and lend support to the notion that MUTYH mutations increase the risk of developing HNPCC related diseases. There was no difference in the five genotype frequencies of the endometrial cancer

  19. Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer.

    Science.gov (United States)

    Guntupalli, Saketh R; Zighelboim, Israel; Kizer, Nora T; Zhang, Qin; Powell, Matthew A; Thaker, Premal H; Goodfellow, Paul J; Mutch, David G

    2012-01-01

    Adjuvant radiotherapy improves local control but not survival in women with endometrial cancer. This benefit was shown in staged patients with "high intermediate risk" (HIR) disease. Other studies have challenged the need for systematic staging including lymphadenectomy. We sought to determine whether LVSI alone or in combination with other histologic factors predicts lymph node (LN) metastasis in patients with endometrioid endometrial cancer. A retrospective review was conducted of patients with endometrioid endometrial carcinoma who had confirmed presence/absence of LVSI and clinicopathologic data necessary to identify HIR criteria. Kaplan-Meier curves were generated and univariate and multivariate analyses performed as appropriate. We identified 757 eligible patients and 628 underwent systematic lymphadenectomy for staging purposes. In the surgically staged group, 242 (38%) patients met uterine HIR criteria and 196 (31%) had LVSI. Both HIR and LVSI were significantly associated with LN metastasis. Among the HIR positive group, 59 had LN metastasis (OR 4.46, 95% CI 2.72-7.32, PHIR negative specimens was 95.6% and 93.4% respectively. In multivariate analysis, PFS and OS were significantly reduced in both LVSI positive (PHIR patients (PHIR negative. HIR status and LVSI are highly associated with LN metastasis. These features are useful in assessing risk of metastatic disease and may serve as a surrogate for prediction of extrauterine disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cilla, Savino, E-mail: savinocilla@gmail.com [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Macchia, Gabriella [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Sabatino, Domenico [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Digesù, Cinzia; Deodato, Francesco [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Piermattei, Angelo [Physics Institute, Università Cattolica del Sacro Cuore, Rome (Italy); De Spirito, Marco [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Morganti, Alessio G. [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Radiation Oncology Unit, Università Cattolica del Sacro Cuore, Rome (Italy)

    2013-04-01

    The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in this analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.

  1. Cigarette smoking and endometrial cancer risk: the modifying effect of obesity.

    Science.gov (United States)

    Polesel, Jerry; Serraino, Diego; Zucchetto, Antonella; Lucenteforte, Ersilia; Dal Maso, Luigino; Levi, Fabio; Negri, Eva; Montella, Maurizio; Franceschi, Silvia; Talamini, Renato; La Vecchia, Carlo

    2009-11-01

    The objective of this study was to evaluate the association between cigarette smoking and endometrial cancer risk by investigating potential modifying effects of menopausal status, obesity, and exogenous hormones. We pooled data from three case-control studies with the same study design conducted in Italy and Switzerland between 1982 and 2006. Overall, 1446 incident endometrial cancers and 4076 hospital controls were enrolled. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, conditioned on study and centre, and adjusted for age, period of interview, age at menarche, parity, and body mass index. In comparison with never smokers, current smokers showed reduced endometrial cancer risk (OR: 0.80; 95% CI: 0.66-0.96), with a 28% decrease in risk for smoking ≥ 20 cigarettes/day. The association did not vary according to menopausal status, oral contraceptive use, or hormone replacement therapy. However, heterogeneity emerged according to body mass index among postmenopausal women, with obese women showing the greatest risk reduction for current smoking (OR: 0.47; 95% CI: 0.27-0.81). In postmenopausal women, obesity turned out to be an important modifier of the association between cigarette smoking and the risk of endometrial cancer. This finding calls for caution in interpreting the favorable effects of cigarette smoking, considering the toxic and carcinogenic effects of tobacco.

  2. Loss of p27 Associated with Risk for Endometrial Carcinoma Arising in the Setting of Obesity.

    Science.gov (United States)

    McCampbell, A S; Mittelstadt, M L; Dere, R; Kim, S; Zhou, L; Djordjevic, B; Soliman, P T; Zhang, Q; Wei, C; Hursting, S D; Lu, K H; Broaddus, R R; Walker, C L

    2016-01-01

    Endometrial carcinoma (EC) exhibits the strongest association with obesity of all cancers. Growth of these tumors is driven by PI3K/AKT activation, and opposed by tumor suppressors, including the tuberous sclerosis complex 2 (TSC-2) and p27, with inactivation of TSC2 and loss or cytoplasmic mislocalization of p27 both being linked to PI3K/AKT activation. However, little is known about the involvement of p27 in the development of EC arising in the setting of obesity, especially its role early in disease progression. Using a panel of EC cell lines, in vitro studies using PI3K inhibitors provided evidence that p27 rescue contributes to the efficacy of interventions that inhibit endometrial cell growth. In "at risk" obese patients, and in an animal model of obesity-associated EC (Tsc2-deficient Eker rats), p27 was moderately-to-severely reduced in both "normal" endometrial glands as well as in endometrial complex atypical hyperplasia (obese women), and endometrial hyperplasia (obese rats). In obese Eker rats, an energy balance intervention; caloric restriction from 2-4 months of age, reduced weight, increased adiponectin and lowered leptin to produce a favorable leptin:adiponectin ratio, and reduced circulating insulin levels. Caloric restriction also increased p27 levels, relocalized this tumor suppressor to the nucleus, and significantly decreased hyperplasia incidence. Thus, dietary and pharmacologic interventions that inhibit growth and decrease risk for development of endometrial lesions are associated with increased expression and nuclear (re)localization of p27. These data suggest that p27 levels and localization may be useful as a biomarker, and possible determinant, of risk for EC arising in the setting of obesity.

  3. Childhood body mass index and height and risk of histologic subtypes of endometrial cancer

    DEFF Research Database (Denmark)

    Aarestrup, J.; Gamborg, M.; Ulrich, L. G.

    2016-01-01

    BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer....... METHODS: From the Copenhagen School Health Records Register, 155 505 girls born 1930-1989 with measured weights and heights from 7 to 13 years were linked to health registers. BMI and height were transformed to age-specific z-scores. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox...

  4. Long-term dietary heme iron and red meat intake in relation to endometrial cancer risk

    NARCIS (Netherlands)

    Genkinger, J.M.; Friberg, E.; Goldbohm, R.A.; Wolk, A.

    2012-01-01

    Background: Heme and total iron, present in meat, have been hypothesized to promote carcinogenesis. Few prospective studies have examined the associations between intakes of heme and total iron, types of meat, and endometrial cancer risk. Objective: We evaluated the associations between intakes of

  5. Reduced risk of breast, endometrial and ovarian cancer in women with celiac disease.

    Science.gov (United States)

    Ludvigsson, Jonas F; West, Joe; Ekbom, Anders; Stephansson, Olof

    2012-08-01

    Women with celiac disease (CD) may be at decreased risk of female hormone-related cancers given the observed reduction in breast cancer seen in some cohorts. Using biopsy data from all 28 pathology departments in Sweden, we identified 17,852 women with CD who were diagnosed between 1969 and 2007. We used Cox regression model to estimate their risk of breast, endometrial and ovarian cancer and then compared them with 88,400 age- and sex-matched controls. The results indicate that individuals with CD were at a lower risk for all three outcomes: breast cancer (hazard ratio, HR = 0.85; 95% CI = 0.72-1.01), endometrial cancer (HR = 0.60; 95% CI =0.41-0.86) and ovarian cancer (HR = 0.89; 95% CI =0.59-1.34). This inverse relationship was strengthened when we excluded the first year of follow-up beyond CD diagnosis (breast: HR = 0.82; 95% CI =0.68-0.99; endometrial: HR = 0.58; 0.39-0.87; ovarian cancer: HR = 0.72; 0.45-1.15). In conclusion, CD seems to be inversely related not only to breast cancer but also to endometrial and ovarian cancer. Potential explanations include shared risk factors and early menopause. Copyright © 2011 UICC.

  6. Alcohol consumption, cigarette smoking, and endometrial cancer risk: Results from the Netherlands Cohort Study

    NARCIS (Netherlands)

    Loerbroks, A.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2007-01-01

    Objective: To examine the association between alcohol consumption, cigarette smoking, and endometrial cancer. Methods: In 1986, the Netherlands Cohort Study was initiated. A self-administered questionnaire on dietary habits and other cancer risk factors was completed by 62,573 women. Follow-up for

  7. Loss of p27 Associated with Risk for Endometrial Carcinoma Arising in the Setting of Obesity

    Science.gov (United States)

    McCampbell, Adrienne S.; Mittelstadt, Megan L.; Dere, Ruhee; Kim, Sunam; Zhou, Lijun; Djordjevic, Bojana; Soliman, Pamela T.; Zhang, Qian; Wei, Caimiao; Hursting, Stephen D.; Lu, Karen H.; Broaddus, Russell R.; Walker, Cheryl Lyn

    2017-01-01

    Endometrial carcinoma (EC) exhibits the strongest association with obesity of all cancers. Growth of these tumors is driven by PI3K/AKT activation, and opposed by tumor suppressors, including the tuberous sclerosis complex 2 (TSC-2) and p27, with inactivation of TSC2 and loss or cytoplasmic mislocalization of p27 both being linked to PI3K/AKT activation. However, little is known about the involvement of p27 in the development of EC arising in the setting of obesity, especially its role early in disease progression. Using a panel of EC cell lines, in vitro studies using PI3K inhibitors provided evidence that p27 rescue contributes to the efficacy of interventions that inhibit endometrial cell growth. In “at risk” obese patients, and in an animal model of obesity-associated EC (Tsc2-deficient Eker rats), p27 was moderately-to-severely reduced in both “normal” endometrial glands as well as in endometrial complex atypical hyperplasia (obese women), and endometrial hyperplasia (obese rats). In obese Eker rats, an energy balance intervention; caloric restriction from 2–4 months of age, reduced weight, increased adiponectin and lowered leptin to produce a favorable leptin:adiponectin ratio, and reduced circulating insulin levels. Caloric restriction also increased p27 levels, relocalized this tumor suppressor to the nucleus, and significantly decreased hyperplasia incidence. Thus, dietary and pharmacologic interventions that inhibit growth and decrease risk for development of endometrial lesions are associated with increased expression and nuclear (re)localization of p27. These data suggest that p27 levels and localization may be useful as a biomarker, and possible determinant, of risk for EC arising in the setting of obesity. PMID:26917264

  8. Long-chain ω-3 fatty acid intake and endometrial cancer risk in the Women's Health Initiative.

    Science.gov (United States)

    Brasky, Theodore M; Rodabough, Rebecca J; Liu, Jingmin; Kurta, Michelle L; Wise, Lauren A; Orchard, Tonya S; Cohn, David E; Belury, Martha A; White, Emily; Manson, JoAnn E; Neuhouser, Marian L

    2015-04-01

    Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n-3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk. We examined whether intakes of LCω-3PUFAs were associated with endometrial cancer risk overall and stratified by body size and histologic subtype. Women were n = 87,360 participants of the Women's Health Initiative Observational Study and Clinical Trials who were aged 50-79 y, had an intact uterus, and completed a baseline food-frequency questionnaire. After 13 y of follow-up, n = 1253 incident invasive endometrial cancers were identified. Cox regression models were used to estimate HRs and 95% CIs for the association of intakes of individual ω-3 fatty acids and fish with endometrial cancer risk. Intakes of individual LCω-3PUFAs were associated with 15-23% linear reductions in endometrial cancer risk. In women with body mass index (BMI; in kg/m(2)) endometrial cancer risk (HR: 0.59; 95% CI: 0.40, 0.82; P-trend = 0.001), whereas there was little evidence of an association in overweight or obese women. The reduction in risk observed in normal-weight women was further specific to type I cancers. Long-chain ω-3 intake was associated with reduced endometrial cancer risk only in normal-weight women. Additional studies that use biomarkers of ω-3 intake are needed to more accurately estimate their effects on endometrial cancer risk. This trial was registered at clinicaltrials.gov as NCT00000611. © 2015 American Society for Nutrition.

  9. Dairy Products Intake and Endometrial Cancer Risk: A Meta-Analysis of Observational Studies.

    Science.gov (United States)

    Li, Xiaofan; Zhao, Jing; Li, Peiqin; Gao, Ying

    2017-12-28

    Observational studies have suggested inconsistent findings on the relationship between dairy products intake and endometrial cancer risk. This study aimed to conduct a meta-analysis to evaluate this correlation; moreover, databases including PubMed, ISI Web of Science, and Embase were screened for relevant studies up to 26 February 2017. The inverse variance weighting method and random effects models were used to calculate the overall OR (odds ratio) values and 95% confidence interval (CI). A total of 2 cohort study and 16 case-control studies were included in the current analysis. No significant association was observed between endometrial cancer risk and the intake of total dairy products, milk, or cheese for the highest versus the lowest exposure category (total dairy products (14 studies): OR 1.04, 95% CI: 0.97-1.11, I² = 73%, p = 0.000; milk (6 studies): 0.99, 95% CI: 0.89-1.10, I² = 0.0%, p = 0.43; cheese (5 studies): 0.89, 95% CI: 0.76-1.05, I² = 39%, p = 0.16). The only cohort study with a total of 456,513 participants reported a positive association of butter intake with endometrial cancer risk (OR = 1.14; 95% CI = 1.03-1.26, I² = 2.6%, p = 0.31). There was a significant negative association of dairy products intake and endometrial cancer risk among women with a higher body mass index (BMI) (5 studies, OR 0.66, 95% CI = 0.46-0.96, I² = 75.8%, p = 0.002). Stratifying the analyses by risk factors including BMI should be taken into account when exploring the association of dairy products intake with endometrial cancer risk. Further well-designed studies are needed.

  10. Body size over the life-course and the risk of endometrial cancer: the California Teachers Study.

    Science.gov (United States)

    Horn-Ross, Pamela L; Canchola, Alison J; Bernstein, Leslie; Deapen, Dennis; Lacey, James V; Lee, Eunjung; Nelson, David O; Reynolds, Peggy

    2016-12-01

    Obesity is a public health epidemic and a major risk factor for endometrial cancer. Here, we identify key aspects of body size which jointly, over the life-course (since adolescence), are associated with endometrial cancer risk. Among 88,142 participants in the California Teachers Study, 887 were diagnosed with invasive type 1 endometrial cancer between 1997-1998 and 2012. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI) for endometrial cancer associated with life-course body size phenotypes, which incorporated validated measures. Among women currently using hormone therapy, endometrial cancer risk was only associated with height (HR 1.78, 95% CI 1.32-2.40 for ≥67 vs. obese in adolescence (HR 4.33, 95% CI 2.51-7.46) or who became overweight/obese as adults (HR 4.74, 95% CI 2.70-8.32) were at greatest risk. Considering absolute body mass, changes in adiposity over time, and body fat distribution together, instead of each measure alone, we identified lifetime obesity phenotypes associated with endometrial cancer risk. These results more clearly define specific risk groups, and may explain inconsistent findings across studies, improve risk prediction models, and aid in developing targeted interventions for endometrial cancer.

  11. A Prospective Cohort Study of Coffee Consumption and Risk of Endometrial Cancer over a 26-year of Follow-Up

    Science.gov (United States)

    Je, Youjin; Hankinson, Susan E.; Tworoger, Shelley S.; DeVivo, Immaculata; Giovannucci, Edward

    2011-01-01

    Background Coffee has been reported to lower levels of estrogen and insulin, two hormones implicated in endometrial carcinogenesis, but prospective data on the relation between coffee consumption and risk of endometrial cancer are limited. Methods We prospectively assessed coffee consumption in relation to endometrial cancer risk in the Nurses’ Health Study (NHS) with 67,470 female participants aged 34–59 in 1980. Cumulative average coffee intake was calculated with all available questionnaires to assess long-term effects. Cox regression models were used to calculate incidence rate ratios (RR), controlling for other risk factors. Results Fewer than 4 cups of coffee per day were not associated with endometrial cancer risk. However, women who consumed 4 or more cups of coffee had 25% lower risk of endometrial cancer than those who consumed less than 1 cup per day (multivariable RR=0.75; 95% CI =0.57–0.97; Ptrend = 0.02). We found the similar association with caffeinated coffee consumption (RR for ≥ 4 vs. coffee consumption, a suggestive inverse association was found among women who consumed 2 or more cups per day vs. coffee per day are associated with a lower risk of endometrial cancer. Impact Drinking of coffee, given its widespread consumption, might be an additional strategy to reduce endometrial cancer risk. However, addition of substantial sugar and cream to coffee could offset any potential benefits. PMID:22109346

  12. A prospective cohort study of coffee consumption and risk of endometrial cancer over a 26-year follow-up.

    Science.gov (United States)

    Je, Youjin; Hankinson, Susan E; Tworoger, Shelley S; De Vivo, Immaculata; Giovannucci, Edward

    2011-12-01

    Coffee has been reported to lower levels of estrogen and insulin, two hormones implicated in endometrial carcinogenesis, but prospective data on the relation between coffee consumption and risk of endometrial cancer are limited. We prospectively assessed coffee consumption in relation to endometrial cancer risk in the Nurses' Health Study (NHS) with 67,470 female participants aged 34 to 59 in 1980. Cumulative average coffee intake was calculated with all available questionnaires to assess long-term effects. Cox regression models were used to calculate incidence rate ratios (RR), controlling for other risk factors. Fewer than 4 cups of coffee per day were not associated with endometrial cancer risk. However, women who consumed 4 or more cups of coffee had 25% lower risk of endometrial cancer than those who consumed less than 1 cup per day (multivariable RR = 0.75; 95% CI = 0.57-0.97; P(trend) = 0.02). We found the similar association with caffeinated coffee consumption (RR for ≥4 vs. coffee consumption, a suggestive inverse association was found among women who consumed 2 or more cups per day versus coffee per day are associated with a lower risk of endometrial cancer. Drinking of coffee, given its widespread consumption, might be an additional strategy to reduce endometrial cancer risk. However, addition of substantial sugar and cream to coffee could offset any potential benefits.

  13. Endometrial Hyperplasia

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Endometrial Hyperplasia Home For Patients Search FAQs Endometrial Hyperplasia ... Spanish Endometrial Hyperplasia FAQ147, May 2011 PDF Format Endometrial Hyperplasia Gynecologic Problems What is endometrial hyperplasia? How ...

  14. Overweight, obesity and endometrial cancer risk: results from a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Yuanyuan; Liu, Huaizhen; Yang, Shengjie; Zhang, Jinjun; Qian, Liwei; Chen, Xiaowen

    2014-03-24

    Findings from recent studies suggest that obesity may be associated with an increased risk of endometrial cancer, but several earlier studies were less conclusive. Here we strive to estimate this relationship in a meta-analysis of published data. We searched Pubmed and Embase for studies on body mass index and the risk of endometrial cancer, published from 1989 to 2011. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending on the degree of heterogeneity. Seven cohort studies and 11 case-control studies were included in the meta-analysis. Overall, the conditions of excess body weight ([EBW] defined as body mass index [BMI] ≥25 kg/m²), obesity (BMI ≥30 kg/m²) and overweight (25endometrial cancer (relative risk [RR] for EBW=1.62, 95% confidence interval [CI], 1.39-1.89; for obesity RR=2.54, 95% CI, 2.11-3.06; for overweight RR=1.32, 95% CI, 1.16-1.50). Subgroup analyses showed that the positive associations were independent of study design, geographic locations, self-reported BMI, alcohol use, smoking habit, history of diabetes, hormone therapy, age at menarche, age at menopause, parity, and age at first full term pregnancy. However, there was no statistically significant association between EBW and endometrial cancer risk for measured BMI (for EBW RR=1.29, 95% CI, 0.66-2.53). The findings from this meta-analysis strongly support that the conditions of EBW, overweight, and obesity are all associated with an increased risk of endometrial cancer. Also, the strength of the association increases with increasing BMI.

  15. HNF1B and endometrial cancer risk: results from the PAGE study.

    Directory of Open Access Journals (Sweden)

    Veronica Wendy Setiawan

    Full Text Available We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC and the Women's Health Initiative (WHI as part of the Population Architecture using Genomics and Epidemiology (PAGE study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls. The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs per allele and 95% confidence intervals (CIs of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ≥ 0.21 or between studies (P ≥ 0.70. The OR(per allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6 for rs4430796 (G allele and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7 for rs7501939 (A allele. The associations with the risk of Type I and Type II tumors were similar (P ≥ 0.19. Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.

  16. Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial.

    Science.gov (United States)

    Trabert, Britton; Eldridge, Ronald C; Pfeiffer, Ruth M; Shiels, Meredith S; Kemp, Troy J; Guillemette, Chantal; Hartge, Patricia; Sherman, Mark E; Brinton, Louise A; Black, Amanda; Chaturvedi, Anil K; Hildesheim, Allan; Berndt, Sonja I; Safaeian, Mahboobeh; Pinto, Ligia; Wentzensen, Nicolas

    2017-02-01

    Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score. Of 64 markers, 22 were associated with endometrial cancer risk at p inflammation score categories. Endometrial cancer risk was most pronounced among obese women with the highest inflammation score tertile (T) [10.25 (3.56-29.55) vs. normal BMI/T1]. Several inflammation markers were prospectively associated with endometrial cancer, including adipokines, pro- and anti-inflammatory cytokines, angiogenic factors and acute phase proteins. Inverse associations with anti-inflammatory markers (IL13, IL21), other inflammation markers/mediators (CCL3, IL1B, IL23), and a robust positive association between VEGFA and endometrial cancer risk were independent of BMI and estradiol, suggesting that these factors may influence risk through other mechanisms. © 2016 UICC.

  17. Sugar-sweetened beverage intake and the risk of type I and type II endometrial cancer among postmenopausal women.

    Science.gov (United States)

    Inoue-Choi, Maki; Robien, Kim; Mariani, Andrea; Cerhan, James R; Anderson, Kristin E

    2013-12-01

    Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women's Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the Surveillance Epidemiology and End Results Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for body mass index (BMI) and other cofounders (Ptrend = 0.0005). Compared with nondrinkers of SSB, the risk was 78% higher [95% confidence intervals (CI), 1.32-2.40] among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Higher intake of SSB and sugars was associated with an increased risk of type I, but not type II, endometrial cancer. SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. ©2013 AACR.

  18. Concurrent Endometrial Carcinoma in Patients with a Curettage Diagnosis of Endometrial Hyperplasia

    OpenAIRE

    Chen, Yu-Li; Cheng, Wen-Fang; Lin, Ming-Chieh; Huang, Chia-Yen; Hsieh, Chang-Yao; Chen, Chi-An

    2009-01-01

    Endometrial hyperplasia is considered a precursor of endometrial carcinoma, but concurrent endometrial carcinoma in patients with endometrial hyperplasia is seen frequently. Our aim was to examine the risk factors for coexisting endometrial carcinoma in patients with endometrial hyperplasia. Methods: Between January 1996 and September 2006, 77 patients who underwent hysterectomy for endometrial hyperplasia were enrolled retrospectively. We divided the patients into non-endometrial carcinom...

  19. Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre-versus post-operative risk stratification

    NARCIS (Netherlands)

    Eggink, F A; Mom, C H; Bouwman, K; Boll, D; Becker, J H; Creutzberg, C L; Niemeijer, G C; van Driel, W J; Reyners, A K; van der Zee, A G; Bremer, G L; Ezendam, N P; Kruitwagen, R F; Pijnenborg, J M; Hollema, H; Nijman, H W; van der Aa, M.A.

    Background: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival. Methods: Patients diagnosed with EC

  20. Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre- versus post-operative risk stratification

    NARCIS (Netherlands)

    Eggink, F.A.; Mom, C.H.; Bouwman, K.; Boll, D.; Becker, J.H.; Creutzberg, C.L.; Niemeijer, G.C.; Driel, W.J. van; Reyners, A.K.; Zee, A.G. van der; Bremer, G.L.; Ezendam, N.P.; Kruitwagen, R.F.P.M.; Pijnenborg, J.M.A.; Hollema, H.; Nijman, H.W.; Aa, M.A. van der

    2017-01-01

    BACKGROUND: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival. METHODS: Patients diagnosed with EC

  1. Genetic polymorphisms in obesity-related genes and endometrial cancer risk.

    Science.gov (United States)

    Chen, Xiaoli; Xiang, Yong-Bing; Long, Ji-Rong; Cai, Hui; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2012-07-01

    Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin (ADIPOQ), leptin (LEP), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), and leptin receptor (LEPR) are associated with endometrial cancer. The authors selected 87 tagging SNPs to capture common genetic variants in these 5 genes. These SNPs were evaluated in 1028 endometrial cancer cases and 1932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI, 0.48-0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ, which were in linkage disequilibrium with rs3774262. These associations became nonsignificant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, smaller waist and hip circumferences, and lower body mass index than controls with the major allele G (all P cancer risk. Although a chance finding cannot be ruled out, the consistency of findings for gene-endometrial cancer risk and gene-obesity measurements suggests that genetic polymorphisms in the ADIPOQ gene may play a role in endometrial cancer development. Copyright © 2011 American Cancer Society.

  2. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis.

    Science.gov (United States)

    Verdoodt, F; Kjaer, S K; Friis, S

    2017-06-01

    Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and prognosis of ovarian and endometrial cancer. The evidence of a preventive effect of NSAID use on risk of ovarian or endometrial cancer is based primarily on results from observational studies and, consequently, is only suggestive. Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Body Size, Metabolic Factors, and Risk of Endometrial Cancer in Black Women.

    Science.gov (United States)

    Sponholtz, Todd R; Palmer, Julie R; Rosenberg, Lynn; Hatch, Elizabeth E; Adams-Campbell, Lucile L; Wise, Lauren A

    2016-02-15

    Total and abdominal obesity, as well as metabolic factors such as type 2 diabetes, have been associated with a higher risk of endometrial cancer in white women. It remains unclear to what extent these factors influence the risk of endometrial cancer in black women. We followed 47,557 participants from the Black Women's Health Study for incident endometrial cancer from 1995 through 2013 (n = 274). We used Cox regression models to estimate incidence rate ratios and 95% confidence intervals while accounting for potential confounders. Incidence rate ratios for body mass indices (weight (kg)/height (m)(2)) of 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40.0 versus those endometrial cancer among black women and appeared to explain most of the associations seen with other adiposity measures and metabolic factors. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Risk Factors for Unsuccessful Office-Based Endometrial Biopsy: A Comparative Study of Office-Based Endometrial Biopsy (Pipelle) and Diagnostic Dilation and Curettage.

    Science.gov (United States)

    Xie, Bingying; Qian, Cuifeng; Yang, Bingyi; Ning, Chengcheng; Yao, Xiaoying; Du, Yan; Shi, Yue; Luo, Xuezhen; Chen, Xiaojun

    2017-12-06

    To determine the risk factors for Pipelle diagnostic failure, which might help healthcare providers choose the appropriate protocol for endometrial evaluation individually. A single-center prospective study (Canadian Task Force classification II). The Obstetrics and Gynecology Hospital of Fudan University. Patients (n = 466) with an indication for endometrial biopsy. All patients received Pipelle and then diagnostic dilation and curettage. The samples were sent for histopathologic diagnosis separately. The Pipelle procedure failed in 10 of 466 patients (2.146%). The general sample inadequacy and histopathologic diagnosis inconsistency of Pipelle was 5.921% (27/456) and 14.254% (65/456), respectively. Upon multivariate analysis, history of cervical operation(s) (odds ratio [OR], 26.510; 95% coefficient interval [CI], 2.932-239.784; p = .004), prior intrauterine procedure(s) (OR, .096; 95% CI, .017-.554; p = .009), and pinpoint cervical os (OR, 5.939; 95% CI, 1.134-31.108; p = .035) were significantly associated with Pipelle procedure failure. Meanwhile, uterine volume endometrial cancer cases, whereas only 50.000% (7/14) of endometrial hyperplasia with atypia, 26.471% (9/34) of polyps, and 18.182% (2/11) of polyps with endometrial hyperplasia without atypia cases were detected by Pipelle. Although Pipelle is the first-line method for endometrial biopsy, it might fail in women with risk factors identified in this study. More considerations should be taken when choosing Pipelle. Copyright © 2018. Published by Elsevier Inc.

  5. Type I and II Endometrial Cancers: Have They Different Risk Factors?

    Science.gov (United States)

    Setiawan, Veronica Wendy; Yang, Hannah P.; Pike, Malcolm C.; McCann, Susan E.; Yu, Herbert; Xiang, Yong-Bing; Wolk, Alicja; Wentzensen, Nicolas; Weiss, Noel S.; Webb, Penelope M.; van den Brandt, Piet A.; van de Vijver, Koen; Thompson, Pamela J.; Strom, Brian L.; Spurdle, Amanda B.; Soslow, Robert A.; Shu, Xiao-ou; Schairer, Catherine; Sacerdote, Carlotta; Rohan, Thomas E.; Robien, Kim; Risch, Harvey A.; Ricceri, Fulvio; Rebbeck, Timothy R.; Rastogi, Radhai; Prescott, Jennifer; Polidoro, Silvia; Park, Yikyung; Olson, Sara H.; Moysich, Kirsten B.; Miller, Anthony B.; McCullough, Marjorie L.; Matsuno, Rayna K.; Magliocco, Anthony M.; Lurie, Galina; Lu, Lingeng; Lissowska, Jolanta; Liang, Xiaolin; Lacey, James V.; Kolonel, Laurence N.; Henderson, Brian E.; Hankinson, Susan E.; Håkansson, Niclas; Goodman, Marc T.; Gaudet, Mia M.; Garcia-Closas, Montserrat; Friedenreich, Christine M.; Freudenheim, Jo L.; Doherty, Jennifer; De Vivo, Immaculata; Courneya, Kerry S.; Cook, Linda S.; Chen, Chu; Cerhan, James R.; Cai, Hui; Brinton, Louise A.; Bernstein, Leslie; Anderson, Kristin E.; Anton-Culver, Hoda; Schouten, Leo J.; Horn-Ross, Pamela L.

    2013-01-01

    Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed. PMID:23733771

  6. Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Aune, D; Navarro Rosenblatt, D A; Chan, D S M; Vingeliene, S; Abar, L; Vieira, A R; Greenwood, D C; Bandera, E V; Norat, T

    2015-08-01

    Greater body mass index (BMI) has been convincingly related to increased endometrial cancer risk, however, whether adiposity earlier in life or abdominal fatness is an independent risk factor and whether weight gain or greater height increases the risk is not clear. As part of the Continuous Update Project of the World Cancer Research Fund International, we conducted a systematic review and meta-analysis of prospective studies of the association between anthropometric measures and endometrial cancer risk and searched PubMed and several other databases up to February 2015. Summary relative risks (RRs) were calculated using a random-effects model. Thirty prospective studies of BMI and endometrial cancer risk with 22 320 cases among 6 445 402 participants were included. The summary RR for a 5-unit increment was 1.54 [95% confidence interval (CI) 1.47-1.61, I(2) = 81%]. Although the test for non-linearity was significant, Pnon-linearity obese BMI ranges, there was evidence of increased risk even within the high normal BMI range. The summary RR was 1.45 (95% CI 1.28-1.64, I(2) = 76%) per 5 BMI units for BMI in young adulthood, 1.18 (95% CI 1.14-1.23, I(2) = 67%) per 5 kg increase of weight, and 1.16 (95% CI 1.12-1.20, I(2) = 51%) per 5 kg of weight gained between young adulthood and study baseline, 1.27 (95% CI 1.17-1.39, I(2) = 71%) per 10 cm increase in waist circumference, 1.21 (95% CI 1.13-1.29, I(2) = 0%) per 0.1-unit increment in waist-to-hip ratio and 1.30 (95% CI 1.19-1.41, I(2) = 0%) per 10-cm increase in hips circumference. The summary RR was 1.15 (95% CI 1.09-1.22, I(2) = 61%) for a 10-cm increase in height. All measures of adiposity were associated with increased risk of endometrial cancer, and in addition increasing height was associated with increased risk. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Improved outcome of high grade, early 1 stage endometrioid endometrial carcinoma with adjuvant chemotherapy and radiotherapy : Comparison of 2 treatment strategies

    NARCIS (Netherlands)

    Reynaers, Eline Aem; Jutzi, Leah; Ezendam, N.P.M.; Kwon, Janice S.; Pijnenborg, Johanna M.a.

    2017-01-01

    Objective: patients with high grade endometrioid endometrial carcinoma have a high risk of recurrence, even in early stage. To determine the benefit of a more aggressive adjuvant treatment approach, different treatment strategies of 2 referral centers were compared. Materials and methods: outcome of

  8. Improved Outcome of High-Grade, Early 1-Stage Endometrioid Endometrial Carcinoma With Adjuvant Chemotherapy and Radiotherapy: Comparison of 2 Treatment Strategies

    NARCIS (Netherlands)

    Reynaers, E.A.; Jutzi, L.; Ezendam, N.P.; Kwon, J.S.; Pijnenborg, J.M.A.

    2017-01-01

    OBJECTIVE: Patients with high-grade endometrioid endometrial carcinoma have a high risk of recurrence, even in early stage. To determine the benefit of a more aggressive adjuvant treatment approach, different treatment strategies of 2 referral centers were compared. MATERIALS AND METHODS: Outcome of

  9. Endometrial adenocarcinoma after endometrial ablation. A case report

    OpenAIRE

    Areia, AL; Branco, M; Frutuoso, C; Oliveira, CF

    2006-01-01

    The authors present a case of endometrial adenocarcinoma after endometrial ablation, emphasizing the importance of close surveillance of these patients, patient selection and education. Even patients with none of the risk factors for endometrial cancer or contraindications to endometrial ablation should be checked carefully.

  10. Lymph node dissection in atypical endometrial hyperplasia.

    Science.gov (United States)

    Taşkın, Salih; Kan, Özgür; Dai, Ömer; Taşkın, Elif A; Koyuncu, Kazibe; Alkılıç, Ayşegül; Güngör, Mete; Ortaç, Fırat

    2017-09-01

    The rate of concomitant endometrial carcinoma in patients with atypical endometrial hyperplasia is high. We aimed to investigate the role of lymphadenectomy in deciding adjuvant treatment in patients with concomitant atypical endometrial hyperplasia and endometrial carcinoma. Women with atypical endometrial hyperplasia were enrolled in this retrospective study. Lymph node dissection was performed in only some patients who gave informed consent if their surgeon elected to do so, or if the intraoperative findings necessitated. The final histopathologic evaluations of surgical specimens were compared with endometrial biopsy results. Eighty eligible patients were evaluated. Seventy-two (90%) patients had complex hyperplasia with atypia, and 8 (10%) patients had simple hyperplasia with atypia. Hysterectomy and bilateral salpingo-oophorectomy were performed to all patients; 37 also underwent lymph node dissection. Lymph node dissection was extended to the paraaortic region in 9 of 37 patients. The concomitant endometrial carcinoma rate was 50%. Two patients had lymph node metastasis. Among 40 cases of carcinoma, 17 had deep myometrial invasion and/or cervical or ovarian involvement or grade 2 tumors with superficial myometrial invasion on hysterectomy specimens; 27.5% of all carcinomas were stage Ib or higher. The concomitant endometrial carcinoma rate was high in patients with atypical endometrial hyperplasia. Nearly half of these patients had risk factors for extrauterine spread. Lymph node dissection might be helpful to decide adjuvant treatment.

  11. Obesity and Endometrial Cancer.

    Science.gov (United States)

    Shaw, Eileen; Farris, Megan; McNeil, Jessica; Friedenreich, Christine

    Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and endometrial cancer risk, while severe obesity (BMI > 35 kg/m(2)) was associated with a 4.7-fold increase compared to normal-weight women (BMI endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.

  12. High stathmin expression is a marker for poor clinical outcome in endometrial cancer: An NRG oncology group/gynecologic oncology group study.

    Science.gov (United States)

    Reyes, Henry D; Miecznikowski, Jeffrey; Gonzalez-Bosquet, Jesus; Devor, Eric J; Zhang, Yuping; Thiel, Kristina W; Samuelson, Megan I; McDonald, Megan; Stephan, Jean-Marie; Hanjani, Parviz; Guntupalli, Saketh; Tewari, Krishnansu S; Backes, Floor; Ramirez, Nilsa; Fleming, Gini F; Filiaci, Virginia; Birrer, Michael J; Leslie, Kimberly K

    2017-08-01

    Gynecologic Oncology Group (GOG) 177 demonstrated that addition of paclitaxel to a backbone of adriamycin/cisplatin improves overall survival (OS) and progression-free survival (PFS) for patients with advanced or recurrent endometrial cancer. Using patient specimens from GOG-177, our objective was to identify potential mechanisms underlying the improved clinical response to taxanes. Stathmin (STMN1) is a recognized poor prognostic marker in endometrial cancer that functions as a microtubule depolymerizing protein, allowing cells to transit rapidly through mitosis. Therefore, we hypothesized that one possible mechanism underlying the beneficial effects of paclitaxel could be to counter the impact of stathmin. We analyzed the expression of stathmin by immunohistochemistry (IHC) in 69 specimens from patients enrolled on GOG-177. We also determined the correlation between stathmin mRNA expression and clinical outcomes in The Cancer Genome Atlas (TCGA) dataset for endometrial cancer. We first established that stathmin expression was significantly associated with shorter PFS and OS for all analyzed cases in both GOG-177 and TCGA. However, subgroup analysis from GOG-177 revealed that high stathmin correlated with poor PFS and OS particularly in patients who received adriamycin/cisplatin only. In contrast, there was no statistically significant association between stathmin expression and OS or PFS in patients treated with paclitaxel/adriamycin/cisplatin. Our findings demonstrate that high stathmin expression is a poor prognostic marker in endometrial cancer. Paclitaxel may help to negate the impact of stathmin overexpression when treating high risk endometrial cancer cases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Preoperative risk stratification using metabolic parameters of {sup 18}F-FDG PET/CT in patients with endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, Kazuhiro [Kobe University School of Medicine, Department of Radiology, Kobe (Japan); Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan); Suenaga, Yuko; Ueno, Yoshiko; Maeda, Tetsuo; Sofue, Keitarou; Sugimura, Kazuro [Kobe University School of Medicine, Department of Radiology, Kobe (Japan); Ebina, Yasuhiko; Yamada, Hideto [Kobe University School of Medicine, Department of Obstetrics and Gynecology, Kobe (Japan); Okunaga, Takashi; Kubo, Kazuhiro [Kobe University Hospital, Department of Radiology Division, Kobe (Japan); Kanda, Tomonori [Teikyo University School of Medicine, Department of Radiology, Tokyo (Japan); Tamaki, Yukihisa [Shimane University School of Medicine, Department of Radiation Oncology, Shimane (Japan)

    2015-07-15

    To evaluate the usefulness of metabolic parameters obtained by {sup 18}F-FDG PET/CT for preoperative stratification of high-risk and low-risk endometrial carcinomas. Preoperative {sup 18}F-FDG PET/CT was performed in 56 women with endometrial cancer. Maximum standardized uptake values (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumours were compared with clinicopathological features of surgical specimens. Diagnostic performance in terms of differentiation of low-risk disease (endometrioid histology, histological grade 1 or 2, invasion of less than half of the myometrium, and FIGO stage I) from high-risk disease was assessed. MTV and TLG were significantly higher in patients with higher histological grade (p = 0.0026 and p = 0.034), larger tumour size (p = 0.002 and p = 0.0017), lymphovascular space involvement (LVSI; p = 0.012 and p = 0.0051), myometrial invasion (p = 0.027 and p = 0.031), cervical stromal invasion (p = 0.023 and p = 0.014), ovarian metastasis (p = 0.00022 and p = 0.00034), lymph node metastasis (p < 0.0001 and p < 0.0001), and higher FIGO stage (p = 0.0011 and p = 0.00048). SUVmax was significantly higher in patients with larger tumour size (p = 0.0025), LVSI (p = 0.00023) and myometrial invasion (p < 0.0001). The areas under the ROC curves (AUCs) for distinguishing high-risk from low-risk carcinoma were 0.625, 0.829 and 0.797 for SUVmax, MTV and TLG, respectively. AUCs for both MTV and TLG were significantly larger than that for SUVmax (p = 0.0049 and p = 0.021). The optimal TLG cut-off value of 70.2, determined by ROC analysis, was found to have 72.0 % sensitivity and 74.2 % specificity for risk stratification. MTV and TLG of primary endometrial cancer show better correlations with clinicopathological features and are more useful for differentiating high-risk from low-risk carcinoma than SUVmax. (orig.)

  14. Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer: a nationwide case-control study.

    Science.gov (United States)

    Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian; Kjaer, Susanne K

    2015-07-01

    We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age-matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated. We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70-0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82-0.99). We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some indications of risk reductions associated with low-dose aspirin use among nulliparous women and with non-aspirin NSAID use among women having used HRT.

  15. Modelling body mass index and endometrial cancer risk in a pooled-analysis of three case-control studies.

    Science.gov (United States)

    Rota, M; Rumi, F; Bagnardi, V; Dal Maso, L; Zucchetto, A; Levi, F; La Vecchia, C; Tavani, A

    2016-01-01

    To quantify the relation between body mass index (BMI) and endometrial cancer risk, and to describe the shape of such a relation. Pooled analysis of three hospital-based case-control studies. Italy and Switzerland. A total of 1449 women with endometrial cancer and 3811 controls. Multivariate odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from logistic regression models. The shape of the relation was determined using a class of flexible regression models. The relation of BMI with endometrial cancer. Compared with women with BMI 18.5 to endometrial cancer and suggest that the risk in obese women increases in a cubic nonlinear fashion. The relation was stronger in never-users of oral contraceptives and in women with diabetes. © 2015 Royal College of Obstetricians and Gynaecologists.

  16. Lymphedema after treatment for endometrial cancer - A review of prevalence and risk factors.

    Science.gov (United States)

    Lindqvist, Emma; Wedin, Madelene; Fredrikson, Mats; Kjølhede, Preben

    2017-04-01

    Lymphedema is one of the least studied complications of cancer treatment and a chronic condition with a substantial impact on health-related quality of life (HQoL). Lymphedema of the legs (LLL) constitutes a common adverse side effect of lymphadenectomy LA in gynecologic cancer treatment. Primary treatment of endometrial cancer (EC) comprises hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic lymphadenectomy is recommended in prognostic high risk groups of EC. This review summarizes the published literature concerning the prevalence of LLL after treatment for EC, methods used for measuring LLL, risk factors and HQoL impact. The main findings are that the reported prevalence of LLL varies significantly between 0% and 50%. This is due to a lack of a generally accepted standardization of terminology in assessment of lymphedema. The studies use different methods to assess and grade lymphedema and often the methodology used for determining LLL is poorly described and lacks baseline measurement. Lymphadenectomy, number of lymph nodes removed, and radiation therapy seems to increase the risk for LLL. All studies dealing with HQoL show that women with LLL have impaired HQoL. The level of evidence in the published studies is generally low. Consequently it is difficult to make clear-cut conclusions about the true prevalence or determination of risk factors. More prospective longitudinal or randomized trials with LLL as the primary outcome are necessary before conclusions can be drawn regarding prevalence of LLL and risk factor determination in EC. An internationally accepted standardization for terminology and methodology in lymphedema in research is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. OBESITY IN RELATION TO ENDOMETRIAL CANCER RISK AND DISEASE CHARACTERISTICS IN THE WOMEN’S HEALTH INITIATIVE

    Science.gov (United States)

    Reeves, Katherine W.; Carter, Gebra Cuyun; Rodabough, Rebecca J.; Lane, Dorothy; McNeeley, S. Gene; Stefanick, Marcia L.; Paskett, Electra D.

    2011-01-01

    Objective Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer. Methods We studied 86,937 postmenopausal women enrolled in the Women’s Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade. Results During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Though incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade. Conclusions Obesity increases endometrial cancer risk independent of other factors, but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival. PMID:21324514

  18. The modifying effect of C-reactive protein gene polymorphisms on the association between central obesity and endometrial cancer risk.

    Science.gov (United States)

    Wen, Wanqing; Cai, Qiuyin; Xiang, Yong-Bing; Xu, Wang-Hong; Ruan, Zhi Xian; Cheng, Jiarong; Zheng, Wei; Shu, Xiao-Ou

    2008-06-01

    Obesity is a major risk factor for endometrial cancer. Obesity, particularly central obesity, is considered as a systemic inflammatory condition and is related strongly to insulin resistance. C-reactive protein (CRP) is the most recognized biologic marker of chronic systematic inflammation, and it is conceivable that the CRP gene may work together with obesity in the development of endometrial cancer. On the basis of a population-based case-control study in a Chinese population, the authors obtained obesity measurements and data on 6 CRP single-nucleotide polymorphisms (SNPs) from 1046 patients with newly diagnosed endometrial cancer (cases) and from 1035 age frequency-matched controls. The association of the CRP SNPs with endometrial cancer risk and their modification on the association between obesity and endometrial cancer risk were evaluated. Although CRP SNPs alone were not associated with endometrial cancer, the associations of endometrial cancer with central obesity, measured as the waist-to-hip ratio (WHR) and the waist circumference, seemed to be stronger in women who were homozygous for the major allele of reference SNP (rs)1130864 (cytidine [C]/C) than in women who had the C/thymidine (T) and T/T genotypes (interaction test: P = .013 for WHR; P = .083 for waist circumference). When the women were stratified further by menopausal status, the observed interactions persisted mainly in premenopausal women (interaction test: P obesity-related insulin resistance and proinflammatory effects may play an important role in endometrial cancer risk, and these effects were modified significantly by the CRP SNP rs1130864. (c) 2008 American Cancer Society.

  19. Coffee Decreases the Risk of Endometrial Cancer: A Dose–Response Meta-Analysis of Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Alessandra Lafranconi

    2017-11-01

    Full Text Available Aim: The aim of this study was to perform a comprehensive meta-analysis of the association between coffee consumption and risk of endometrial cancer. Methods: Eligible studies were identified by searching the PubMed and EMBASE databases. The dose–response relationship as well as the risk of endometrial cancer for the highest versus the lowest categories of coffee consumption were assessed. Subgroup analyses considering the menopausal and receptor statuses, the smoking status, and the BMI (Body Mass Index were performed in order to identify potential confounders. Results: We identified a total of 12 studies eligible for meta-analysis. A dose–response meta-analysis showed a decreased risk of endometrial cancer. Moreover, a subgroup analysis indicated that coffee consumption is significantly associated with a decreased risk of postmenopausal cancer. Increasing coffee consumption by four cups per day was associated with a 20% reduction in endometrial cancer risk (relative risk (RR 0.80; 95% confidence interval (CI 0.72 to 0.89 and with a 24% reduction in postmenopausal cancer risk (RR 0.76; 95% CI 0.69 to 0.83. Conclusions: Our findings suggest that increased coffee consumption is associated with decreased risk of endometrial cancer, and this association is observed also for postmenopausal cancer.

  20. Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes

    NARCIS (Netherlands)

    Xu, Bei; Geerts, Dirk; Bu, Zhiqin; Ai, Jihui; Jin, Lei; Li, Yufeng; Zhang, Hanwang; Zhu, Guijin

    2014-01-01

    Are other HOX genes, in addition to HOXA10, involved in endometrial receptivity? The highly expressed HOXA9, HOXA11 and HOXD10 genes also appear to be involved in endometrial receptivity. Within the HOX family of homeobox transcription factor genes are the leading candidates for the regulation of

  1. Cadmium exposure and endometrial cancer risk: A large midwestern U.S. population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Jane A McElroy

    Full Text Available Estrogen-mimicking chemicals, such as cadmium, may be associated with increased susceptibility to hormone-dependent cancers, though supporting data are sparse, particularly for endometrial cancer. The Health and Environmental Exposure Research (HEER study worked with the Arkansas Central Cancer Registry, Iowa Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed with endometrial cancer who were willing to be contacted for participation in our case control study. Voter registration lists from Iowa and Missouri were used to randomly select similarly aged women as represented in the case population. Participants were interviewed by telephone to obtain information on known or suspected endometrial risk factors. Urine kits were sent to participants for home collection and returned for analysis. Our case-control study consisted of 631 incident cases of endometrial cancer diagnosed from January 2010 to October 2012 and 879 age-matched population-based controls, ages 18-81 years (mean age 65 years. We quantified cadmium amounts in urine and standardized these values through creatinine adjustment. Using data from all survey completers, we developed a multivariable model for endometrial cancer. Creatinine-adjusted cadmium concentration was added to this model. Odds ratio (OR and 95% confidence intervals (CIs for endometrial cancer were calculated. After multivariable adjustment, higher creatinine-adjusted cadmium exposure was associated with a statistically significant increase of endometrial cancer risk (OR: 1.22; 95% CI: 1.03-1.44. Our results provide evidence that cadmium may increase the risk of endometrial cancer, possibly through estrogenic effects.

  2. Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico.

    Science.gov (United States)

    Salazar-Martinez, E; Lazcano-Ponce, E; Sanchez-Zamorano, L M; Gonzalez-Lira, G; Escudero-DE Los Rios, P; Hernandez-Avila, M

    2005-01-01

    Daily diet factors that could potentially be related to endometrial cancer (EC) in Mexico are still unknown. This study aims to evaluate the association between EC and Mexican dietary factors. A case-control study in Mexico City was conducted during 1995-1997 in a social security hospital, using 85 incident cases of EC and 629 controls. A validated questionnaire with 116 items about the frequency and type of food intake was used. The analysis of nutrients was performed using the residual method, adjusting by predictor variables through logistic regression methods. In addition, partitional models estimated total caloric intake for other sources. We found no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of nutrients such as lactose (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21-1.01, P for trend = 0.004), vitamin D (OR, 0.38; 95% CI, 0.18-0.82, P= 0.003), and calcium (OR, 0.39; 95% CI, 0.17-0.89, P= 0.02) were inversely associated with EC. Our results suggest that dietary vitamin D and calcium play an important role in the development of EC, although the mechanisms postulated should be explained with additional studies with large populations.

  3. Understanding obesity and endometrial cancer risk: opportunities for prevention

    National Research Council Canada - National Science Library

    Schmandt, Rosemarie E; Iglesias, David A; Co, Ngai Na; Lu, Karen H

    2011-01-01

    Worldwide, obesity has become a major public health crisis. Overweight and obesity not only increase the risk of cardiovascular disease and type-2 diabetes mellitus but also are now known risk factors for a variety of cancer types...

  4. Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors.

    Science.gov (United States)

    Merritt, Melissa A; Strickler, Howard D; Einstein, Mark H; Yang, Hannah P; Sherman, Mark E; Wentzensen, Nicolas; Brouwer-Visser, Jurriaan; Cossio, Maria Jose; Whitney, Kathleen D; Yu, Herbert; Gunter, Marc J; Huang, Gloria S

    2016-06-01

    Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data. Endometrial tissue mRNA and protein levels were measured using quantitative real-time PCR and immunohistochemistry, respectively. In postmenopausal women, we observed higher levels of phosphorylated IGF-I/insulin receptor (pIGF1R/pIR) in diabetic versus non-diabetic women (p value =0.02), while women who reported regular nonsteroidal anti-inflammatory drug use versus no use had higher levels of insulin and progesterone receptors (both p values ≤0.03). We also noted differences in pIGF1R/pIR staining with OC use (postmenopausal women only), and the proportion of estrogen receptor-positive tissues varied by the number of live births and PTEN status (premenopausal only) (p values ≤0.04). Compared to premenopausal proliferative phase women, postmenopausal women exhibited lower mRNA levels of IGF1, but higher IGFBP1 and IGFBP3 expression (all p values ≤0.004), and higher protein levels of the receptors for estrogen, insulin, and IGF-I (all p values ≤0.02). Conversely, pIGF1R/pIR levels were higher in premenopausal proliferative phase versus postmenopausal endometrium (p value =0.01). These results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis.

  5. Risk of spilling cancer cells during total laparoscopic hysterectomy in low-risk endometrial cancer

    Directory of Open Access Journals (Sweden)

    Satoshi Shinohara

    2017-08-01

    Conclusion: We conclude that fallopian tubal cauterization is sufficient to provide protection from the dissemination of cancer cells into the peritoneal cavity at the time of TLH for endometrial cancers in early stages.

  6. The unrecognized burden of cardiovascular risk factors in women newly diagnosed with endometrial cancer: A prospective case control study.

    Science.gov (United States)

    Kitson, Sarah J; Lindsay, Jennifer; Sivalingam, Vanitha N; Lunt, Mark; Ryan, Neil A J; Edmondson, Richard J; Rutter, Martin K; Crosbie, Emma J

    2018-01-01

    Cardiovascular disease is a major cause of death in endometrial cancer survivors. The aim of this study was to determine whether women newly diagnosed with endometrial cancer have a higher prevalence of cardiovascular risk factors than the general population. The prevalence of adequately treated and unrecognized/inadequately treated cardiovascular risk factors and the corresponding 10-year cardiovascular risk by QRISK2 score was measured in 150 consecutive women undergoing primary treatment for endometrioid endometrial cancer in the North West of England, and 746 age and ethnicity-matched control women from the Health Survey for England 2014. Women with endometrial cancer had higher proportions of obesity (BMI≥30 60.7% vs. 32.4%, pendometrial cancer cases had a higher prevalence of incident hyperglycemia (57.2%vs.11.5%, p4.5 (26.7%vs.13.7%, pendometrial cancer have a higher prevalence of cardiovascular risk factors than women without the disease. Early identification and treatment of these risk factors could improve outcomes for endometrial cancer survivors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

    Science.gov (United States)

    Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

    2015-11-01

    Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, pendometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The risk of lymphedema after postoperative radiation therapy in endometrial cancer

    Science.gov (United States)

    Catalano, Paul J.; Cimbak, Nicole; Muto, Michael G.; Viswanathan, Akila N.

    2016-01-01

    Objective Lower extremity lymphedema adversely affects quality of life by causing discomfort, impaired mobility and increased risk of infection. The goal of this study is to investigate factors that influence the likelihood of lymphedema in patients with endometrial cancer who undergo adjuvant radiation with or without chemotherapy. Methods A retrospective chart review identified all stage I–III endometrial cancer patients who had a hysterectomy with or without complete staging lymphadenectomy and adjuvant radiation therapy between January 2006 and February 2013. Patients with new-onset lymphedema after treatment were identified. Logistic regression was used to find factors that influenced lymphedema risk. Results Of 212 patients who met inclusion criteria, 15 patients (7.1%) developed new-onset lymphedema. Lymphedema was associated with lymph-node dissection (odds ratio [OR], 5.6; 95% CI, 1.01 to 105.5; p=0.048) and with the presence of pathologically positive lymph nodes (OR, 4.1; 95% CI, 1.4 to 12.3; p=0.01). Multivariate logistic regression confirmed the association with lymph-node positivity (OR, 3.2; 95% CI, 1.0007 to 10.7; p=0.0499) when controlled for lymph-node dissection. Median time to lymphedema onset was 8 months (range, 1 to 58 months) with resolution or improvement in eight patients (53.3%) after a median of 10 months. Conclusion Lymph-node positivity was associated with an increased risk of lymphedema in endometrial cancer patients who received adjuvant radiation. Future studies are needed to explore whether node-positive patients may benefit from early lymphedema-controlling interventions. PMID:26463430

  9. Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.

    Science.gov (United States)

    Fortner, Renée T; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Peeters, Petra H M; Weiderpass, Elisabete; Gram, Inger T; Gavrilyuk, Oxana; Quirós, J Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Allen, Naomi E; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-03-15

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination. © 2016 UICC.

  10. "Assessment of endometrial cancer risk factors in a pilot study at Vali-e-Asr unit, Imam Khomeini hospital "

    Directory of Open Access Journals (Sweden)

    "Ghaemmaghamei F

    2001-05-01

    Full Text Available This study was performed to identify endometrial Cancer risk factors. In a case series study on 1989-1996 , we assessed endometrial cancer in 52 patients whose age range was 32-80 years, with 73% over fifty years. Obesity was seen in 68% at time of cancer detection , and 69% were in the postmenopausal age, with a history of late menopause in 21%. As a matter of parity 13% were nulliparous, and 52% were grandmultiparous. There was a history of hypertension in 37% and ovarian tumors and polyeystic ovaian disease in 2%. The most common symptom in our patients was vaginal bleeding and the most frequent histology was endometrioid adenocarcinoma. Endometrial cancer was most common in the sirth decade of age. The two most common risk factors in this population were obesity and hypertension. The next important risk factor was late menopause.

  11. Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer.

    Science.gov (United States)

    Painter, Jodie N; O'Mara, Tracy A; Marquart, Louise; Webb, Penelope M; Attia, John; Medland, Sarah E; Cheng, Timothy; Dennis, Joe; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley V; Beckmann, Matthias W; Ekici, Arif B; Fasching, Peter A; Hein, Alexander; Rübner, Matthias; Czene, Kamila; Darabi, Hatef; Hall, Per; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Lambrechts, Diether; Neven, Patrick; Cunningham, Julie M; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie A; Otton, Geoffrey; Proietto, Anthony; Mints, Miriam; Tham, Emma; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2016-11-01

    The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10-17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44-1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10-1.39; P = 5.3 × 10-4). There was evidence of directional pleiotropy (P = 1.5 × 10-4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10-4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503-10. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

    Science.gov (United States)

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

    2017-07-01

    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as

  13. The role of human epididymis secretory protein E4 in patients with endometrial cancer and premalignant endometrial lesions.

    Science.gov (United States)

    Yılmaz, Setenay Arzu; Altınkaya, Sündüz Özlem; Kerimoglu, Özlem Seçilmiş; Tazegül Pekin, Aybike; Akyürek, Fikret; Ilhan, Tolgay Tuyan; Benzer, Nilgün; Unlu, Ali; Yuksel, Hasan; Celik, Cetin

    2017-01-01

    We evaluated the concentrations of human epididymis secretory protein E4 (HE4) and Ca-125 in relation to clinicopathologic features in patients with endometrial cancer and premalignant endometrial lesions. Women with abnormal uterine bleeding (n = 167) who underwent endometrial sampling were divided into four groups. Group 1: endometrial cancer (n = 68), group 2: atypical endometrial hyperplasia (n = 12), group 3: endometrial hyperplasia without atypia (n = 39) and group 4: controls (n = 48). Women with endometrial cancer exhibited higher concentrations of HE4 levels than controls (91.4 pmol/L vs. 46.2 pmol/L, p endometrial cancer were 72.7%, 84.4%, 80% and 78.4%, respectively. Preoperative HE4 levels are more elevated in women with endometrial cancer than those with benign endometrium as well as in women with prognostic high-risk factors with endometrial cancer. HE4 may be used as an additional marker in combination with other clinicopathologic features for planning the treatment.

  14. Medically inoperable endometrial cancer in patients with a high body mass index (BMI): Patterns of failure after 3-D image-based high dose rate (HDR) brachytherapy.

    Science.gov (United States)

    Acharya, Sahaja; Esthappan, Jacqueline; Badiyan, Shahed; DeWees, Todd A; Tanderup, Kari; Schwarz, Julie K; Grigsby, Perry W

    2016-01-01

    High BMI is a reason for medical inoperability in patients with endometrial cancer in the United States. Definitive radiation is an alternative therapy for these patients; however, data on patterns of failure after definitive radiotherapy are lacking. We describe the patterns of failure after definitive treatment with 3-D image-based high dose rate (HDR) brachytherapy for medically inoperable endometrial cancer. Forty-three consecutive patients with endometrial cancer FIGO stages I-III were treated definitively with HDR brachytherapy with or without external beam radiation therapy. Cumulative incidence of failures was estimated and prognostic variables were identified Mean follow up was 29.7 months. Median BMI was 50.2 kg/m(2) (range: 25.1-104 kg/m(2)). The two-year overall survival was 65.2%. The two-year cumulative incidence of pelvic and distant failures was 8.3% and 13.5%, respectively. Grade 3 disease was associated with a higher risk of all-failures (Hazard Ratio [HR]: 4.67, 95% CI: 1.04-20.9, p=0.044). The incidence of acute Grade 3 GI/GU toxicities was 4.6%. Pelvic failure at two years was less than 10%. Patients with grade 3 disease were more likely to experience disease failure and may warrant closer follow up. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Evaluation of the Risk of Spreading Endometrial Cell by Hysteroscopy: A Prospective Longitudinal Study

    Directory of Open Access Journals (Sweden)

    Rievani de Sousa Damião

    2009-01-01

    Results. Four patients were excluded for presenting endometrial cells in PW1. In the 72 patients left, there was no passage of cells for the peritoneal cavity. In group 1, 88% presented secretory endometrial phase with correlation of 80% between hysteroscopy and biopsy. Conclusion. Hysteroscopy performed under a low pressure of CO2 does not cause spreading of endometrial cells into the peritoneal cavity.

  16. Human papillomavirus effect on the development of endometrial polyps.

    Science.gov (United States)

    Korucuoglu, U; Guler, I; Dogan, H; Biri, A

    2015-01-01

    Although the association of human papillomavirus (HPV) with warts arising in different parts of the human body has been well-demonstrated, the association of HPV with endometrial polyps has never been studied in the literature up to now. Detection of the HPV DNA was carried out by using 13 high-risk HPV real-time PCR Kit and five low-risk HPV real-time PCR Kit. Among 50 endometrial polyp samples, one endometrial polyp sample revealed a positive result for the presence of HPV type 18. This first study in the medical literature investigating the possible effect of HPV on the development of endometrial polyps has demonstrated that HPV might have a role in the development of some of the endometrial polyps. If the present authors' hypothesis that endometrial polyps caused by carcinogenic HPV types are prone to proceed to endometrial cancer if left untreated is correct, HPV vaccine has a potential to prevent development of at least some of the endometrial polyps and endometrial cancers.

  17. High frequency of RPL22 mutations in microsatellite-unstable colorectal and endometrial tumors.

    Science.gov (United States)

    Ferreira, Ana M; Tuominen, Iina; van Dijk-Bos, Krista; Sanjabi, Bahram; van der Sluis, Tineke; van der Zee, Ate G; Hollema, Harry; Zazula, Monika; Sijmons, Rolf H; Aaltonen, Lauri A; Westers, Helga; Hofstra, Robert M W

    2014-12-01

    Ribosomal Protein L22 (RPL22) encodes a protein that is a component of the 60S subunit of the ribosome. Variants in this gene have recently been linked to cancer development. Mutations in an A8 repeat in exon 2 were found in a recent study in 52% of microsatellite-unstable endometrial tumors. These tumors are particularly prone to mutations in repeats due to mismatch repair deficiency. We screened this coding repeat in our collection of microsatellite-unstable endometrial tumors (EC) and colorectal tumors (CRC). We found 50% mutation frequency for EC and 77% mutation frequency for CRC. These results confirm the previous study on the involvement of RPL22 in EC and, more importantly, reports for the first time such high mutation frequency in this gene in colorectal cancer. Furthermore, considering the high mutation frequency found, our data point toward an important role for RPL22 in microsatellite instability carcinogenesis. © 2014 WILEY PERIODICALS, INC.

  18. Investigation of dietary factors and endometrial cancer risk using a nutrient-wide association study approach in the EPIC and nurses' health study (NHS) and NHSII

    NARCIS (Netherlands)

    Merritt, Melissa A.; Tzoulaki, Ioanna; Tworoger, Shelley S.; De Vivo, Immaculata; Hankinson, Susan E.; Fernandes, Judy; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Tjønneland, Anne; Petersen, Kristina E N; Dahm, Christina C.; Overvad, Kim; Dossus, Laure; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; Fortner, Renée T.; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-De-Mesquita, H. B.; Onland-Moret, N. Charlotte; Peeters, Petra H.; Gram, Inger T.; Skeie, Guri; Quirós, J. Ramón; Duell, Eric J.; Sánchez, María José; Salmerón, D.; Barricarte, Aurelio; Chamosa, Saioa; Ericson, Ulrica; Sonestedt, Emily; Nilsson, Lena Maria; Idahl, Annika; Khaw, Kay Tee; Wareham, Nicholas; Travis, Ruth C.; Rinaldi, Sabina; Romieu, Isabelle; Patel, Chirag J.; Riboli, Elio; Gunter, Marc J.

    2015-01-01

    Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false

  19. Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study.

    Science.gov (United States)

    Uccella, S; Mariani, A; Wang, A H; Vierkant, R A; Robien, K; Anderson, K E; Cerhan, J R

    2011-09-01

    Type I and II endometrial cancer are biologically and clinically distinct, with type II cancers having a high frequency of p53 mutations and an association with chromosomal instability. This raises the hypothesis that one-carbon nutrients (folate, methionine, and the enzymic cofactors vitamins B2, B6, and B12), which mediate chromosomal stability and DNA methylation, may be protective for type II but not type I endometrial cancer. Using a prospective cohort of 23 356 postmenopausal women followed 20 years, we estimated the relative risks (RRs) of type I (N = 471) and II (N = 71) endometrial cancers according to intake of one-carbon nutrients, adjusting for confounders. No associations were observed between dietary or supplemental intake of any one-carbon nutrient and risk of type I cancer. For type II cancer, positive associations were due to supplemental, rather than dietary, intake of these nutrients: supplemental folate (RR = 1.80 for >228.6 versus 0 μg/day; P trend = 0.027) and vitamins B2 (RR = 1.94 for >1.70 versus 0 mg/day; P trend = 0.011), B6 (RR = 2.08 for >2.00 versus 0 mg/day; P trend = 0.012), and B12 (RR = 2.10 for >3.43 versus 0 μg/day; P trend = 0.0060). Contrary to our hypothesis, use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.

  20. Childhood body size and associations with prostate and endometrial cancer risks and adult body size (Ph.D)

    DEFF Research Database (Denmark)

    Aarestrup, Julie

    2015-01-01

    barndommen en periode hvor mekanistiske undersøgelser af disse sammenhænge skal fokusere. Engelsk: Prostate and endometrial cardinogenesis is linked to early life body size, suggesting that these diseases have early origins. Even though these associations may operate through adult body size, it is not likely...... of later prostate and endometrial cancer, childhood may be the period of time that mechanistic investigations should focus on in their search for links between body size and the risk of these cancer forms....

  1. Dietary carbohydrates, glycemic index, glycemic load, and endometrial cancer risk within the European prospective investigation into cancer and nutrition cohort

    NARCIS (Netherlands)

    Cust, Anne E.; Slimani, Nadia; Kaaks, Rudolf; van Bakel, Marit; Biessy, Carine; Ferrari, Pietro; Laville, Martine; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Lajous, Martin; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Linseisen, Jakob; Rohrmann, Sabine; Noethlings, Ute; Boeing, Heiner; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Skeie, Guri; Engeset, Dagrun; Gram, Inger Torhild; Quiros, J. Ramon; Jakszyn, Paula; Sanchez, Maria Jose; Larranaga, Nerea; Navarro, Carmen; Ardanaz, Eva; Wirfalt, Elisabet; Berglund, Goran; Lundin, Eva; Hallmans, Goeran; Bueno-de-Mesquita, H. Bas; Du, Huaidong; Peeters, Petra H. M.; Bingham, Shelia; Khaw, Kay-Tee; Allen, Naomi E.; Key, Timothy J.; Jenab, Mazda; Riboli, Elio

    2007-01-01

    The associations of dietary total carbohydrates, overall glycemic index, total dietary glycemic load, total sugars, total starch, and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospective Investigation into Cancer and Nutrition cohort (1992-2004),

  2. HE4 and CA125 levels in the preoperative assessment of endometrial cancer patients

    DEFF Research Database (Denmark)

    Antonsen, Sofie L; Høgdall, Estrid; Christensen, Ib J

    2013-01-01

    To evaluate whether human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) correlated to known high-risk prognostic factors for endometrial cancer.......To evaluate whether human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) correlated to known high-risk prognostic factors for endometrial cancer....

  3. [OBESITY AND ENDOMETRIAL CARCINOGENESIS].

    Science.gov (United States)

    Uchikova, E; Uchikov, P; Parahuleva, P

    2015-01-01

    Endometrial cancer is one of the main cancers occurring in industrialized countries. According to the National Cancer Registry in Bulgaria, cancer of the uterine body occupies 8.6% from all cancers in women and ranks second in frequency. It is found that over weight and obesity are a major risk factor for the development of endometrial cancer and the mortality associated with it. Adipose tissue is seen as endocrine organ, synthesizing so called adipocytokine - leptin, adiponectin, vistafin, that play a key role in the carcinogenesis of endometrial cancer and can be used as new markers for establishing the potential risk of this disease. The link between obesity, insulin resistance and endometrial cancer that has been proven, determines it as a socially significant disease. All this makes it necessary to clarify and specify the role of obesity in endometrial carcinogenesis and the development of strategies for the prevention and early diagnosis.

  4. Preoperative high dose rate brachytherapy for clinical stage II endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Alexander Olawaiye

    2011-07-01

    Full Text Available Purpose: We sought to evaluate pathological response, tolerance, and outcome after preoperative (neoadjuvant high dose rate brachytherapy in a small series of patients with clinical stage II endometrial carcinoma, and to evaluate a dose and fractionation protocol for this treatment. Material and methods: Twelve women diagnosed with clinical stage II endometrial carcinoma from 1999-2010 were treated with preoperative radiation therapy. Their medical charts were retrospectively analyzed for HDR treatment regimen, pathological response, and longitudinal outcomes. Radiation doses were normalized to a biologically equi­valent dose of 2 Gy per fraction (EQD2. Results: Two patients had complete pathological response to neoadjuvant therapy; five more had only microscopic residual disease at the time of surgery. At a median follow up of 37 months (1-91 months, one patient has developed recurrence at the vaginal apex six months after completing initial therapy, while another developed a lung recurrence at 28 months. Two-year disease-free and cause-specific survivals were 88% and 100%, respectively. Conclusions: Our small study shows that the HDR fractionation schedule, as done in our series for preoperative radiation therapy for clinical stage II endometrial cancer, is well tolerated and would be an option for patients treated with neoadjuvant radiation therapy.

  5. Lifestyle changes and the risk of developing endometrial and ovarian cancers: opportunities for prevention and management

    Directory of Open Access Journals (Sweden)

    Beavis AL

    2016-05-01

    Full Text Available Anna L Beavis,1,* Anna Jo Bodurtha Smith,2,* Amanda Nickles Fader1 1Department of Gynecology and Obstetrics, The Kelly Gynecologic Oncology Service, Johns Hopkins Medicine, Baltimore, MD, 2Harvard Medical School, Boston, MA, USA *These authors contributed equally to this work Abstract: Modifiable lifestyle factors, such as obesity, lack of physical activity, and smoking, contribute greatly to cancer and chronic disease morbidity and mortality worldwide. This review appraises recent evidence on modifiable lifestyle factors in the prevention of endometrial cancer (EC and ovarian cancer (OC as well as new evidence for lifestyle management of EC and OC survivors. For EC, obesity continues to be the strongest risk factor, while new evidence suggests that physical activity, oral contraceptive pills, and bariatric surgery may be protective against EC. Other medications, such as metformin and nonsteroidal anti-inflammatory drugs, may be protective, and interventional research is ongoing. For OC, we find increasing evidence to support the hypothesis that obesity and hormone replacement therapy increase the risk of developing OC. Oral contraceptive pills are protective against OC but are underutilized. Dietary factors such as the Mediterranean diet and alcohol consumption do not seem to affect the risk of either OC or EC. For EC and OC survivors, physical activity and weight loss are associated with improved quality of life. Small interventional trials show promise in increasing physical activity and weight maintenance for EC and OC survivors, although the impact on long-term health, including cancer recurrence and overall mortality, is unknown. Women’s health providers should integrate counseling about these modifiable lifestyle factors into both the discussion of prevention for all women and the management of survivors of gynecologic cancers. Keywords: lifestyle, prevention, endometrial cancer, ovarian cancer, gynecologic cancer, obesity

  6. Coffee consumption and risk of endometrial cancer: findings from a large up-to-date meta-analysis.

    Science.gov (United States)

    Je, Youjin; Giovannucci, Edward

    2012-10-01

    Several epidemiological studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta-analysis of observational studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. A total of 16 studies (10 case-control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62-0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control studies and 0.70 (95% CI: 0.61-0.80) for cohort studies. By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; 95% CI: 0.25-0.63) than five studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60-0.79) or eight studies from Europe (pooled RR = 0.79; 95% CI: 0.63-0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90-0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control studies. More large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk. Copyright © 2011 UICC.

  7. Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

    Science.gov (United States)

    O’Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica MJ; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2015-01-01

    Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3,633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6,607 EC cases and 37,925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P = 1.86 × 10−5), which was stronger for cancers of endometrioid subtype (P = 3.76 × 10−6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. PMID:26330482

  8. Risk Factors Influencing Development Of Surgical Site Infection In Patients Who Were Operated Due To Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Ayse Inci

    2016-06-01

    Full Text Available Endometrial cancer is the most commonly encountered malignancy of female genital system. Surgery is the main treatment approach in endometrial cancer. The frequency of surgical site infections (SSI has recently increased. Prediction of risk factors which may cause SSI and taking due precautions may provide a decrease in frequency of these infections. The aim of this study was to determine the risk factors for SSI after surgery for endometrial cancer. The medical records of patients who were operated due to endometrial cancer in Kanuni Sultan Suleyman Education and Research Hospital between January 1st, 2015 and July 31st, 2015 were retrospectively reviewed. Patients were divided into two groups; those that developed SSI following the operation and those that did not develop SSI. Surgical site infections were diagnosed based on Center for Disease Control and Prevention criteria. Ages, co-morbid diseases, body mass index (BMI, ASA (American Society of Anesthesiologists scores, smoking, durations of operation, presence of drainage, blood transfusion, pre-op hemoglobin level and pre-op glucose level of patients were recorded. A p [Dis Mol Med 2016; 4(2.000: 13-17

  9. Assessment of the effects of severe obesity and lifestyle risk factors on stage of endometrial cancer.

    Science.gov (United States)

    Bittoni, Marisa A; Fisher, James L; Fowler, Jeffrey M; Maxwell, George L; Paskett, Electra D

    2013-01-01

    Lifestyle risk factors, including obesity, have been associated with increased risk of endometrial cancer (EC). Women with higher obesity levels tend to have less aggressive EC disease stage and histology. This study further investigated associations between nonmodifiable risk factors, such as age, race, and grade, and modifiable lifestyle factors, such as diet and physical activity expenditure, in relation to severe obesity and late versus early EC stage at diagnosis. Demographic, anthropometric, and lifestyle surveys were administered to 177 women with histologically confirmed EC. Logistic regression analyses assessed the relationship between obesity and other risk factors on EC stage at diagnosis. In multivariate models, body mass index (BMI) obesity-EC stage association. Our results corroborate those of past studies showing that BMI is not an independent risk factor for EC stage and that age may have confounded the obesity-EC stage association. Because of mixed results and implications for treatment outcomes, however, further research examining these variables is warranted. Our results provide further insight into the obesity EC-stage association, especially the confounding effect of age. Future studies should examine modifiable lifestyle factors in larger and more diverse populations.

  10. Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

    Science.gov (United States)

    Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B

    2017-11-01

    To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10-7), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (PTrend=4.43×10-6), and with increasing numbers of Lynch cancers in relatives (PTrend≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Medically inoperable endometrial cancer in patients with a high body mass index (BMI): Patterns of failure after 3-D image-based high dose rate (HDR) brachytherapy

    DEFF Research Database (Denmark)

    Acharya, Sahaja; Esthappan, Jacqueline; Badiyan, Shahed

    2016-01-01

    BACKGROUND AND PURPOSE: High BMI is a reason for medical inoperability in patients with endometrial cancer in the United States. Definitive radiation is an alternative therapy for these patients; however, data on patterns of failure after definitive radiotherapy are lacking. We describe...... the patterns of failure after definitive treatment with 3-D image-based high dose rate (HDR) brachytherapy for medically inoperable endometrial cancer. MATERIALS AND METHODS: Forty-three consecutive patients with endometrial cancer FIGO stages I-III were treated definitively with HDR brachytherapy...

  12. Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta‐analysis of epidemiologic studies

    National Research Council Canada - National Science Library

    Gong, Ting‐Ting; Wu, Qi‐Jun; Wang, Yong‐Lai; Ma, Xiao‐Xin

    2015-01-01

    ... ) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random...

  13. Family History of Breast Cancer as a Determinant of the Risk of Developing Endometrial and Ovarian Cancers: A Nationwide Cohort Study

    National Research Council Canada - National Science Library

    Kazerouni, N. N

    2002-01-01

    Statement of the problem: Although endometrial and ovarian cancers share some of the same reproductive, hormonal, and genetic risk factors with breast cancer, it is not well established if a family history of breast cancer...

  14. The prevalence of endometrial hyperplasia and endometrial cancer in women with polycystic ovary syndrome or hyperandrogenism

    DEFF Research Database (Denmark)

    Holm, Nina Sofie Lillegaard; Glintborg, Dorte; Andersen, Marianne Skovsager

    2012-01-01

    Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of women...

  15. Tumor necrosis factor (TNF)-alpha, soluble TNF receptors and endometrial cancer risk : the EPIC study

    NARCIS (Netherlands)

    Dossus, Laure; Becker, Susen; Rinaldi, Sabina; Lukanova, Annekatrin; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chabbert-Buffet, Nathalie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Teucher, Birgit; Chang-Claude, Jenny; Pischon, Tobias; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Valanou, Elisavet; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Galasso, Rocco; Redondo, Maria-Luisa; Bonet Bonet, Catalina; Molina-Montes, Esther; Altzibar, Jone M.; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H. Bas; van Duijnhoven, Franzel J. B.; Peeters, Petra H. M.; Onland-Moret, N. Charlotte; Lundin, Eva; Idahl, Annika; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi; Romieu, Isabelle; Fedirko, Veronika; Hainaut, Pierre; Romaguera, Dora; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2011-01-01

    Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-alpha (TNF-alpha), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European

  16. High Nuclear Expression of HDGF Correlates with Disease Progression and Poor Prognosis in Human Endometrial Carcinoma

    Directory of Open Access Journals (Sweden)

    Lijing Wang

    2014-01-01

    Full Text Available Aims. This study examined the correlation between high nuclear expression of hepatoma-derived growth factor (HDGF and clinicopathologic data in endometrial carcinoma (EC, including patient survival. Methods. One hundred and twenty-two endometrial carcinoma (EC patients from 2002 to 2008 were reviewed in the study. HDGF expression in tumor tissues was examined using immunohistochemistry (IHC, and its association with clinicopathological parameters was evaluated. Tumors with 80% or more nuclei staining were regarded as high expression and tumors with less than 80% nuclei staining considered as low expression. Results and Conclusions. Immunohistochemical analysis revealed that HDGF was expressed in both the nucleus and cytoplasm. High nuclear expression of HDGF was positively correlated with FIGO stage (P=0.032, but not associated with other clinical features, such as histological grading or lymph node status. Patients with high expression of HDGF had poorer overall survival rates than those with low expression of HDGF (P=0.001. However, multivariate analyses showed that high nuclear expression of HDGF protein was not an independent predictor of prognosis for EC patients (P=0.111. Our results suggest that high nuclear expression of HDGF is a potential unfavorable factor for the progression and prognosis of EC.

  17. Estrogen and high-fat diet induced alterations in C57BL/6 mice endometrial transcriptome profile.

    Science.gov (United States)

    Cheng, Yali; Lv, Qiaoying; Xie, Bingying; Yang, Bingyi; Shan, Weiwei; Ning, Chengcheng; Li, Bing; Xie, Liying; Gu, Chao; Luo, Xuezhen; Chen, Xiaojun; Zhu, Qin

    2018-01-01

    Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC), but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2) pellet and/or high-fat diet (HFD) for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2 + HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-κB signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another's activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia. © 2018 The authors.

  18. Estrogen and high-fat diet induced alterations in C57BL/6 mice endometrial transcriptome profile

    Directory of Open Access Journals (Sweden)

    Yali Cheng

    2017-12-01

    Full Text Available Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC, but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2 pellet and/or high-fat diet (HFD for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2 + HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-κB signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another’s activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia.

  19. Prediction of lymphatic dissemination in endometrioid endometrial cancer: Comparison of three risk-stratification models in a single-institution cohort.

    Science.gov (United States)

    Tuomi, Taru; Pasanen, Annukka; Leminen, Arto; Bützow, Ralf; Loukovaara, Mikko

    2017-03-01

    To compare the performance characteristics of 3 risk-stratification models, referred to as Mayo, Helsinki and Milwaukee models, in predicting lymphatic dissemination in endometrial cancer. A total of 1052 patients with stage I-III endometrioid endometrial cancer were included in the study. The areas under curve were compared with the receiver operating characteristic curve area comparison test. Chi-square and Fisher exact test were used for comparing categorical variables. The Kaplan-Meier method and multivariable Cox regression models were used for survival analyses. The median follow-up time was 55months (range 1-108). Areas under curve were 0.781, 0.830 and 0.829 for the Mayo, Helsinki (P=0.285 vs. Mayo) and Milwaukee (P=0.292 vs. Mayo) models, respectively, in predicting lymphatic dissemination. The rates of false negatives and false positives were similar for all models. The lymphadenectomy rate decreased in the order of Mayo model (71.5%)>Helsinki model (62.4%)>Milwaukee model (48.8%). In patients with stage I cancer, disease specific survival was better for those who satisfied low-risk criteria according to any of the models. In patients with stage II-III cancer, this difference in survival was significant only for the Milwaukee model. Both lymphatic dissemination and high-risk tumor features as per the risk models were independent predictors of survival. The studied models had a similar accuracy in predicting lymphatic dissemination in endometrial cancer. Lymphadenectomy rate was lowest for the Milwaukee model. Survival analyses suggest that variables included in the models predict patient outcome independently of tumor stage. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Endometrial polyps

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007636.htm Endometrial polyps To use the sharing features on this ... or many polyps. Causes The exact cause of endometrial polyps in women is not known. They tend ...

  1. Risk of endometrial cancer in relation to individual nutrients from diet and supplements.

    Science.gov (United States)

    Biel, Rita K; Csizmadi, Ilona; Cook, Linda S; Courneya, Kerry S; Magliocco, Anthony M; Friedenreich, Christine M

    2011-11-01

    Intake of nutrients may influence the risk of endometrial cancer (EC). We aimed to estimate the association of intake of individual nutrients from food and from food plus supplements with EC occurrence. A population-based case-control study conducted in Canada (2002-2006). Nutrient intakes from food and supplements were assessed using an FFQ. Logistic regression was used to estimate EC risk within quartile levels of nutrient intakes. Incident EC cases (n 506) were identified from the Alberta Cancer Registry, and population controls were frequency- and age-matched to cases (n 981). There existed little evidence of an association with EC for the majority of macronutrients and micronutrients examined. We observed a statistically significant increased risk associated with the highest, compared with the lowest, quartile of intake of dietary cholesterol (multivariable-adjusted OR = 1·51, 95 % CI 1·08, 2·11; P for trend = 0·02). Age-adjusted risk at the highest level of intake was significantly reduced for Ca from food sources (OR = 0·73, 95 % CI 0·54, 0·99) but was attenuated in the multivariable model (OR = 0·82, 95 % CI 0·59, 1·13). When intake from supplements was included in Ca intake, risk was significantly reduced by 28 % with higher Ca (multivariable-adjusted OR = 0·72, 95 % CI 0·51, 0·99, P for trend = 0·04). We also observed unexpected increased risks at limited levels of intakes of dietary soluble fibre, vitamin C, thiamin, vitamin B6 and lutein/zeaxanthin, with no evidence for linear trend. The results of our study suggest a positive association between dietary cholesterol and EC risk and an inverse association with Ca intake from food sources and from food plus supplements.

  2. Validation of REM score to predict endometrial cancer in patients with ultrasound endometrial abnormalities: results of a new independent dataset.

    Science.gov (United States)

    Plotti, Francesco; Capriglione, Stella; Terranova, Corrado; Montera, Roberto; Scaletta, Giuseppe; Lopez, Salvatore; Luvero, Daniela; Gianina, Antonelli; Aloisi, Alessia; Benedetti Panici, Pierluigi; Angioli, Roberto

    2017-05-01

    The risk of endometrial malignancy (REM) score is a model formulated in a previous single-center validation study, which has been shown to predict endometrial cancer in women with ultrasound endometrial abnormalities based on multiple features (clinical, ultrasound and laboratorial). The purpose of this study was to validate the performance of REM score in an external validation setting. A population-based database with patients, who underwent elective hysteroscopy for ultrasound endometrial abnormalities between 2013 and 2016 at Department of Obstetrics and Gynecology of Campus Bio-medico of Rome, was used. Starting from January 2013 to June 2016, 330 patients were enrolled for hysteroscopy. Thirty-two patients were excluded due to Asherman syndrome or cervical stenosis. Therefore, a total of 298 patients were considered for the analysis. Based on pathologic examination, 102 patients were found to have endometrial cancer, and 196 had benign endometrial disease. Using the predefined cutoff of 0.3185, identified in the previous publication, in this independent cohort of patients we correctly classified 93/102 patients with endometrial cancer and 187/196 with benign disease, reporting an overall sensitivity and specificity of 93.9 and 95.4% (PPV = 0.91, NPV = 0.95), respectively. REM score showed a high positive predictive value for endometrial cancer prediction. However, before REM score can be applied in daily clinical practice, data from randomized controlled trials are needed.

  3. Genetic variants in MUTYH are not associated with endometrial cancer risk

    OpenAIRE

    Katie A. Ashton; Proietto, Anthony; Otton, Geoffrey; Symonds, Ian; Scott, Rodney J

    2009-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant inherited predisposition to a number of epithelial cancers, most notably colorectal and endometrial cancer. Outside of the context of Lynch syndrome there is little evidence for an autosomal dominant or recessive condition that predisposes to endometrial cancer. Recently, genetic variants in MUTYH have been associated with a recessive form of colorectal cancer, known as MUTYH associated ...

  4. Genetic variants in MUTYH are not associated with endometrial cancer risk

    OpenAIRE

    Ashton Katie A; Proietto Anthony; Otton Geoffrey; Symonds Ian; Scott Rodney J

    2009-01-01

    Abstract Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant inherited predisposition to a number of epithelial cancers, most notably colorectal and endometrial cancer. Outside of the context of Lynch syndrome there is little evidence for an autosomal dominant or recessive condition that predisposes to endometrial cancer. Recently, genetic variants in MUTYH have been associated with a recessive form of colorectal cancer, known as MUTYH as...

  5. Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus.

    Science.gov (United States)

    Pagani, Isabel; Ghezzi, Silvia; Ulisse, Adele; Rubio, Alicia; Turrini, Filippo; Garavaglia, Elisabetta; Candiani, Massimo; Castilletti, Concetta; Ippolito, Giuseppe; Poli, Guido; Broccoli, Vania; Panina-Bordignon, Paola; Vicenzi, Elisa

    2017-03-10

    Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line together with the induction of interferon-β (IFN-β) and of IFN-stimulated genes. Notably, in vitro decidualization of T-HESC with cyclic AMP and progesterone upregulated the cell surface expression of the ZIKV entry co-receptor AXL and boosted ZIKV replication by ca. 100-fold. Thus, endometrial stromal cells, particularly if decidualized, likely represent a crucial cell target of ZIKV reaching them, either via the uterine vasculature in the viremic phase of the infection or by sexual viral transmission, and a potential source of virus spreading to placental trophoblasts during pregnancy.

  6. Changes in inflammatory endometrial cancer risk biomarkers in individuals undergoing surgical weight loss.

    Science.gov (United States)

    Linkov, Faina; Goughnour, Sharon L; Ma, Tianzhou; Xu, Zhongying; Edwards, Robert P; Lokshin, Anna E; Ramanathan, Ramesh C; Hamad, Giselle G; McCloskey, Carol; Bovbjerg, Dana H

    2017-10-01

    Obesity has been strongly linked to endometrial cancer (EC) risk. A number of potential EC risk biomarkers have been proposed, including heightened pro-inflammatory cytokines and adipokines. To evaluate if bariatric surgery can serve as a means for altering levels of such EC risk biomarkers, we investigated changes in these biomarkers after weight loss. Blood samples were collected pre-operatively and 6months post-operatively in 107 female bariatric surgery patients aged 18-72years. Wilcoxon signed-rank tests were used to compare biomarker levels (measured using xMAP immunoassays) pre- and post-surgery. Normative comparisons were implemented to contrast 6-month post-surgery biomarker levels to levels in a sample of 74 age-matched non-obese women. Linear regression was used to evaluate the relationship between biomarker expression at baseline and 6months post-surgery and the relationship between race and biomarker levels. On average, participants lost 30.15kg (SD: 12.26) after the bariatric intervention. Levels of C-peptide, insulin, CRP, leptin, IL-1Rα, and IL-6 significantly decreased, while levels of SHBG, IGFBP1, and adiponectin significantly increased with weight loss. Normative comparisons showed the levels of SHBG, C-peptide, insulin, IGFBP1, adiponectin, CRP, and TNFα after bariatric intervention approached the level of markers in comparison group. Multiple regression analyses revealed significant relationships between changes in BMI and changes in biomarker levels. The changes in IL-1Rα were significantly associated with race. Our findings demonstrate that normalization of EC risk biomarkers can be achieved with bariatric surgery. Improved understanding of biological mechanisms associated with weight loss may inform preventive strategies for EC. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. FDG PET/CT diagnostic criteria may need adjustment based on MRI to estimate the presurgical risk of extrapelvic infiltration in patients with uterine endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sudo, Satoko; Sakuragi, Noriaki [Hokkaido University Graduate School of Medicine, Department of Gynecology, Sapporo (Japan); Hattori, Naoya; Manabe, Osamu; Hirata, Kenji; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Kitaku, Sapporo (Japan); Kato, Fumi; Mimura, Rie; Magota, Keiichi; Sugimori, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Sapporo (Japan)

    2015-04-01

    The staging of endometrial cancer requires surgery which carries the risk of morbidity. FDG PET/CT combined with anatomical imaging may reduce the number of unnecessary lymphadenectomies by demonstrating the risk of extrapelvic infiltration. The purpose of this study was to optimize FDG PET/CT diagnostic criteria for risk assessment in endometrial cancer after first-line risk triage with MRI. The study population comprised 37 patients who underwent curative surgery for the treatment of endometrial cancer. First, the risk of extrapelvic infiltration was triaged using MRI. Second, multiple glucose metabolic profiles of the primary lesion were assessed with FDG PET/CT, and these were correlated with the histopathological risk of extrapelvic infiltration including lymphovascular space invasion (LVSI) and high-grade malignancy (grades 2 and 3). The results of histological correlation were used to adjust FDG PET/CT diagnostic criteria. Presurgical assessment using MRI was positive for deep (>50 %) myometrial invasion in 17 patients. The optimal FDG PET/CT diagnostic criteria vary depending on the results of MRI. Specifically, SUVmax (≥16.0) was used to indicate LVSI risk with an overall diagnostic accuracy of 88.2 % in patients with MRI findings showing myometrial invasion. High-grade malignancy did not correlate with any of metabolic profiles in this patient group. In the remaining patients without myometrial invasion, lesion glycolysis (LG) or metabolic volume were better indicators of LVSI than SUVmax with the same diagnostic accuracy of 80.0 %. In addition, LG (≥26.9) predicted high-grade malignancy with an accuracy of 72.2 %. Using the optimized cut-off criteria for LVSI, glucose metabolic profiling of primary lesions correctly predicted lymph node metastasis with an accuracy of 73.0 %, which was comparable with the accuracy of visual assessment for lymph node metastasis using MRI and FDG PET/CT. FDG PET/CT diagnostic criteria may need adjustment based on the

  8. Intraperitoneal Fat through GRP78: A Risk Factor for Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Răzvan Ciortea

    2016-01-01

    Full Text Available Introduction. The identification of biological markers that indicate an increased risk for the development or recurrence of endometrial cancer (EC in obese women might be useful for decreasing EC mortality and morbidity. Glucose-regulated protein 78 (GRP78 is a major protein of the endoplasmic reticulum expressed in all normal cells. Overexpression of GRP78 has been reported to be a tumoral biomarker. Increased detection of GRP78 is positively correlated with the tumoral stage and prognosis. This study aimed to identify a correlation between intraperitoneal fat, plasma GRP78 levels, and EC. Materials and Methods. Two groups of patients were included in the study: group I, 44 patients diagnosed with EC, and group II, 44 patients without gynecological pathology or inflammatory disorders. Visceral fat was determined by ultrasound and plasma GRP78 levels were measured. Results. Plasma GRP78 levels were significantly higher in patients with EC compared to the control group. Intraperitoneal fat was in a positive linear correlation with the plasma GRP78 level (p<0.0001. Conclusion. The measurement of the GRP78 level associated with the determination of intraperitoneal fat can be a useful predictor for EC.

  9. Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis.

    Science.gov (United States)

    Hernandez, Adrian V; Pasupuleti, Vinay; Benites-Zapata, Vicente A; Thota, Priyaleela; Deshpande, Abhishek; Perez-Lopez, Faustino R

    2015-12-01

    It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle-Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04-52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08-0.21, p fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Endometrial Cancer Screening

    Science.gov (United States)

    ... Treatment Endometrial Cancer Prevention Endometrial Cancer Screening Research Endometrial Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Endometrial Cancer Key Points Endometrial cancer is a disease ...

  11. Risk of endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia treated with total laparoscopic hysterectomy

    Directory of Open Access Journals (Sweden)

    Katsutoshi Oda

    2016-05-01

    Conclusion: Careful preoperative examinations, including hysteroscopy, might be useful to evaluate the risk of EC. Accordingly, we should be still careful about the possibility of overdiagnosis in patients with AEH.

  12. Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome.

    Science.gov (United States)

    Lu, Karen H; Loose, David S; Yates, Melinda S; Nogueras-Gonzalez, Graciela M; Munsell, Mark F; Chen, Lee-May; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M; Broaddus, Russell R

    2013-08-01

    Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.

  13. SENTINEL LYMPH NODES IN ENDOMETRIAL CANCER

    OpenAIRE

    A. I. Berishvili; O. V. Li; T. M. Kochoyan; N. V. Levkina; R. A. Kerimov; S. B. Polikarpova

    2017-01-01

    Endometrial cancer (EC) typically is treated surgically. Because of the adjuvant treatment implications, complete surgical staging including lymphadenectomy is recommended for high-risk ECs. Sentinel lymph node mapping has the potential to provide information about lymph node metastasis while avoiding potential complications of extended lymph node dissection.

  14. Metformin for endometrial hyperplasia.

    Science.gov (United States)

    Clement, Naomi S; Oliver, Thomas Rw; Shiwani, Hunain; Sanner, Juliane Rf; Mulvaney, Caroline A; Atiomo, William

    2017-10-27

    treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment. We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low-quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16

  15. Cryopreservation and recovery of human endometrial epithelial cells with high viability, purity, and functional fidelity.

    Science.gov (United States)

    Chen, Joseph C; Hoffman, Jacquelyn R; Arora, Ripla; Perrone, Lila A; Gonzalez-Gomez, Christian J; Vo, Kim Chi; Laird, Diana J; Irwin, Juan C; Giudice, Linda C

    2016-02-01

    To develop a protocol for cryopreservation and recovery of human endometrial epithelial cells (eECs) retaining molecular and functional characteristics of endometrial epithelium in vivo. In vitro study using human endometrial cells. University research laboratory. Endometrial biopsies were obtained from premenopausal women undergoing benign gynecologic procedures. Primary eECs were cryopreserved in 1% fetal bovine serum/10% dimethylsulfoxide in Defined Keratinocyte Serum-Free Medium (KSFM). Recovered cells were observed for endometrial stromal fibroblast (eSF) contamination and subsequently evaluated for morphology, gene expression, and functional characteristics of freshly cultured eECs and in vivo endometrial epithelium. Analysis of eEC morphology and the absence of eSF contamination; evaluation of epithelial-specific gene and protein expression; assessment of epithelial polarity. Endometrial epithelial cells recovered after cryopreservation (n = 5) displayed epithelial morphology and expressed E-cadherin (CDH1), occludin (OCLN), claudin1 (CLDN1), and keratin18 (KRT18). Compared with eSF, recovered eECs displayed increased (Phuman endometrial epithelium in vivo. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Dietary carbohydrates, glycemic index, glycemic load, and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition cohort.

    Science.gov (United States)

    Cust, Anne E; Slimani, Nadia; Kaaks, Rudolf; van Bakel, Marit; Biessy, Carine; Ferrari, Pietro; Laville, Martine; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Lajous, Martin; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Linseisen, Jakob; Rohrmann, Sabine; Nöthlings, Ute; Boeing, Heiner; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Skeie, Guri; Engeset, Dagrun; Gram, Inger Torhild; Quirós, J Ramón; Jakszyn, Paula; Sánchez, María José; Larrañaga, Nerea; Navarro, Carmen; Ardanaz, Eva; Wirfält, Elisabet; Berglund, Göran; Lundin, Eva; Hallmans, Göran; Bueno-de-Mesquita, H Bas; Du, Huaidong; Peeters, Petra H M; Bingham, Sheila; Khaw, Kay-Tee; Allen, Naomi E; Key, Timothy J; Jenab, Mazda; Riboli, Elio

    2007-10-15

    The associations of dietary total carbohydrates, overall glycemic index, total dietary glycemic load, total sugars, total starch, and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospective Investigation into Cancer and Nutrition cohort (1992-2004), including 710 incident cases diagnosed during a mean 6.4 years of follow-up. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. There were no statistically significant associations with endometrial cancer risk for increasing quartile intakes of any of the exposure variables. However, in continuous models calibrated by using 24-hour recall values, the multivariable relative risks were 1.61 (95% confidence interval: 1.06, 2.45) per 100 g/day of total carbohydrates, 1.40 (95% confidence interval: 0.99, 1.99) per 50 units/day of total dietary glycemic load, and 1.36 (95% confidence interval: 1.05, 1.76) per 50 g/day of total sugars. These associations were stronger among women who had never used postmenopausal hormone therapy compared with ever users (total carbohydrates p(heterogeneity) = 0.04). Data suggest no association of overall glycemic index, total starch, and total fiber with risk, and a possible modest positive association of total carbohydrates, total dietary glycemic load, and total sugars with risk, particularly among never users of hormone replacement therapy.

  17. The Risk of Lymph-Node Metastasis with Positive Peritoneal Cytology in Endometrial Cancer

    Science.gov (United States)

    Garg, Gunjal; Gao, Feng; Wright, Jason D.; Hagemann, Andrea R.; Zighelboim, Israel; Mutch, David G.; Powell, Matthew A.

    2014-01-01

    Objective To determine the correlation between positive peritoneal cytology (PPC) and lymph node metastasis in patients with endometrial cancer grossly confined to the uterus. Methods Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Only those patients with endometrial cancer grossly confined to the uterus who had undergone a complete staging procedure (lymph-node removal) were included. Statistical analysis used Chi-square test and logistic regression models. Results A total of 22,947 patients were identified. PPC was present in 3.5% of patients. The incidence of lymph node metastasis was significantly higher among patients with PPC compared to those with negative peritoneal cytology for all histologic types examined (pcytology status should continue to inform clinical decision-making in endometrial cancer. PMID:23196758

  18. Analysis of serum level of HE4 and CA125 considering selected risk factors among patients with endometrioid endometrial cancer

    Directory of Open Access Journals (Sweden)

    Nabil Abdalla

    2017-01-01

    Full Text Available The aim of the study : To assess the difference of serum level of HE4 and CA125 among patients with endometrioid endometrial cancer, considering the presence or absence of selected risk factors. Material and methods: A retrospective study of 46 patients, whose serum level of HE4 and CA125 level was documented, admitted to our Clinic because of endometrioid endometrial cancer. The statistical difference of both markers was analyzed considering certain risk factors. Results : In the examined group of patients there was no significant statistical difference of HE4 and CA125 levels among patients with and without the following risk factors: older age, menopausal status, overweight and obesity, hypertension, diabetes, early menarche, and family history of certain cancers. Similar results were obtained within the subgroup of patients with stage I endometrial cancer. Both HE4 and CA125 were significantly higher in premenopausal patients than in those after menopause in the more advanced stages of the disease. The same results were obtained within group of patients with advanced histological grading G2 and G3. In this group, higher levels of CA125 were observed among patients without hypertension. Among patients with histological grade G1 the serum level of HE4 was higher in the group of patients older than 60 years than it was in younger patients. Conclusions : In the examined group of patients serum levels of tumour markers may not be affected by the selected risk factors. Higher HE4 and CA125 levels among premenopausal patients may be an alarming sign of advanced stages and classes of histological grading.

  19. Brain Metastases from Endometrial Carcinoma

    Science.gov (United States)

    Piura, Ettie; Piura, Benjamin

    2012-01-01

    This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

  20. External Pelvic and Vaginal Irradiation Versus Vaginal Irradiation Alone as Postoperative Therapy in Medium-Risk Endometrial Carcinoma-A Prospective Randomized Study

    Energy Technology Data Exchange (ETDEWEB)

    Sorbe, Bengt, E-mail: bengt.sorbe@orebroll.se [Department of Gynecological Oncology, Oerebro University Hospital, Oerebro (Sweden); Horvath, Gyoergy; Andersson, Hakan [Department of Gynecological Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Boman, Karin [Department of Gynecological Oncology, Umea University Hospital, Umea (Sweden); Lundgren, Caroline [Department of Gynecological Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Pettersson, Birgitta [Medical Products Agency, Uppsala (Sweden)

    2012-03-01

    Purpose: To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity. Methods and Materials: Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity. Results: Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone. Conclusions: Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.

  1. Salvage high-dose-rate brachytherapy for isolated vaginal recurrence of endometrial cancer.

    Science.gov (United States)

    Baek, Sungjae; Isohashi, Fumiaki; Yamaguchi, Hiroko; Mabuchi, Seiji; Yoshida, Ken; Kotsuma, Tadayuki; Yamazaki, Hideya; Tanaka, Eiichi; Sumida, Iori; Tamari, Keisuke; Otani, Keisuke; Seo, Yuji; Suzuki, Osamu; Yoshioka, Yasuo; Kimura, Tadashi; Ogawa, Kazuhiko

    We have retrospectively analyzed the outcomes of high-dose-rate (HDR) brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer. From 1997 to 2012, salvage HDR brachytherapy was performed in 43 patients. The median age was 64 years (range, 41-88 years). HDR brachytherapy was performed by interstitial brachytherapy in 34 patients (79%) and by intracavity brachytherapy in nine patients (21%). Seventeen (40%) of the 43 patients were treated with external beam radiotherapy. The median followup period was 58 months (range, 6-179 months). The 5-year overall survival (OS), progression-free survival (PFS), and local control rates (LC) were 84%, 52%, and 78%, respectively. Patients who received brachytherapy with external beam radiotherapy experienced no nodal recurrence (0 of 17 patients), whereas 23% of the patients (6 of 26 patients) who received brachytherapy alone experienced nodal recurrence (p = 0.047). The pathologic grade at the time of initial surgery (G1-2 vs. G3) was found to be a significant prognostic factor for both OS and PFS. The respective 5-year OS was 96% vs. 40% (p brachytherapy vs. intracavity brachytherapy) were significant prognostic factors for LC. The respective 5-year LC was 74% vs. 100% (p = 0.020) and 85% vs. 56% (p = 0.035). HDR brachytherapy is effective and feasible in patients with isolated vaginal recurrence of endometrial cancer. Pathologic grade, age, and modality were significant prognostic factors. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  2. Single nucleotide polymorphism of SREBF-1 gene associated with an increased risk of endometrial cancer in Chinese women.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Qiu

    Full Text Available Elevated levels of sterol regulatory element-binding protein-1 (SREBP-1 have been found in endometrial cancer (EC, suggesting that it is essential to the development of EC. Obesity and diabetes have been established as known risk factors of EC, while SREBF-1 gene polymorphisms have also been found to be associated with obesity and type II diabetes. Therefore, we hypothesize that single nucleotide polymorphism (SNP in SREBF-1 gene may be associated with increased risk of EC.We analyzed the sequence of SREBF-1 in tissue samples from 30 EC cases and 6 benign controls using high throughput method. Based on the primary results, we selected one SNP (rs2297508 as a genetic marker to conduct a hospital-based case-control study with 139 EC cases and 129 benign controls. The samples were examined under the microscope to determine their histopathology prior to the SNP analysis using RT-PCR.Through sequence analysis, we found 10 SNPs of SREBF-1 associated with EC, including 3 new SNPs. Fourteen percent of EC showed the rs2297508 SNP with C allele, while only 7% had the C allele was present in benign controls (p = 0.027, OR = 1.983. Additionally, the C allele was associated with cancer differentiation (p<0.05 and the depth of myometrial invasion (p<0.05.Our study indicates that SNP (rs2297508 of SREBF-1 may serve as a genetic predisposition factor for the development of EC and screening of such genetic marker may be helpful in its early detection.

  3. Adipose tissue concentrations of PCB, HCB, chlordane, PBDE and P,P'-DDE and the risk for endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lindstroem, G.; Bavel, B. van; Bjoernfoth, H. [MTM Research Centre, Oerebro Univ., Oerebro (Sweden); Hardell, L. [Dept. of Oncology, Univ. Hospital, Oerebro (Sweden)

    2004-09-15

    Environmental pollutants with hormonal activity, such as xenoestrogens, have for several years been of concern as potential risk factors for hormone dependant tumors. Impacts of increasing levels of xenoestrogens have been observed in aquatic organisms. In humans concern has been focused on ''endocrine disrupting chemicals'' with either estrogenic or antiestrogenic activities. Some persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), and especially the hydroxylated metabolites, and chlordanes, have been postulated to be endocrine disruptors. PCBs have been shown to reverse gonadal sex in turtle5 and abnormalities of reproductive development has been described in juvenile alligators living in contaminated environment in Florida. Hexachlorobenzene (HCB) has been shown to have endocrine-disrupting properties. Also p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) the most persistent metabolite of p,p'-DDT has been postulated to be an environmental endocrine disruptor. In a case-control study on patients with testicular cancer we found higher concentrations of PCBs, HCB and chlordanes in mothers to cases than in mothers to controls. Similar concentrations were found in cases with testicular cancer as in the population controls. The study gave support to the hypothesis that exposure to endocrine disruptors during the fetal period may be of etiologic importance in the etiology of testicular cancer. Another hormone dependent cancer is endometrial cancer. It accounted for 5.8% of all cancers incidents among Swedish women in 2002. The cumulative probability of developing the disease before 85 years of age was 2.8% in 2002. Estrogen replacement has been suggested as a risk factor among several others. The first cases of endometrial cancer among women using estrogen replacement therapy were reported in early 1960's. Is there a relationship between levels of POPs and incidence rate? The aim is to investigate

  4. Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis.

    Science.gov (United States)

    Neill, Annette S; Nagle, Christina M; Protani, Melinda M; Obermair, Andreas; Spurdle, Amanda B; Webb, Penelope M

    2013-03-01

    Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population-based case-control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta-analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta-analysis risk estimates were pooled using a random-effects model. In our case-control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63-0.97]. There was a significant inverse dose-response (p-trend endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta-analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79-0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m(2) ) was 0.72 (0.58-0.90) but there was no association for non-obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women. Copyright © 2012 UICC.

  5. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Barry, John A; Azizia, Mallika M; Hardiman, Paul J

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women. We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated. From 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P cancer (OR, 4.05; 95% CI, 2.42-6.76, P cancer (OR, 2.52; 95% CI, 1.08-5.89, P cancer (OR, 0.78; 95% CI, 0.46-1.32, P cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias

  6. A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer

    NARCIS (Netherlands)

    Hogervorst, J.G.; Schouten, L.J.; Konings, E.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2007-01-01

    Background: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial,

  7. Awareness of the association between obesity and peri-operative risk among newly diagnosed patients with complex atypical hyperplasia and endometrial cancer

    Directory of Open Access Journals (Sweden)

    Lindsay M. Kuroki

    2015-04-01

    Conclusions: Pre-operative counseling for obese women with newly diagnosed endometrial cancer should incorporate more focused education about obesity-related risks. They report being knowledgeable about the risks associated with their surgery; however, more than a quarter are unaware of the impact obesity has on respiratory problems, thromboembolism, wound infection, heart attack or longer operating time and hospital stay.

  8. Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

    Science.gov (United States)

    2013-01-23

    Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

  9. Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study.

    Science.gov (United States)

    Seagle, Brandon-Luke L; Shilpi, Arunima; Buchanan, Samuel; Goodman, Chelain; Shahabi, Shohreh

    2017-08-01

    To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1-22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17-1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

    Science.gov (United States)

    Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

    2015-01-01

    Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with

  11. Ultrasound characteristics of endometrial cancer as defined by the International Endometrial Tumor Analysis (IETA) consensus nomenclature - A prospective multicenter study.

    Science.gov (United States)

    Epstein, Elisabeth; Fischerova, Daniela; Valentin, Lil; Testa, Antonia Carla; Franchi, Dorella; Sladkevicius, Povilas; Frühauf, Filip; Lindqvist, Pelle G; Mascilini, Floriana; Fruscio, Robert; Haak, Lucia Anna; Opolskiene, Gina; Pascual, Maria Angela; Alcazar, Juan Luis; Chiappa, Valentina; Guerriero, Stefano; Carlson, Joseph; Van Holsbeke, Caroline; Leone, Francesco Paolo Giuseppe; De Moor, Bart; Bourne, Tom; van Calster, Ben; Installe, Arnaud; Timmerman, Dirk; Verbakel, Jan Y; Van den Bosch, Thierry

    2017-09-25

    To describe the sonographic features of endometrial cancer in relation to stage, grade, and histological type using the International Endometrial Tumor Analysis (IETA) terminology. Prospective multicenter study on 1714 women with endometrial cancer undergoing a standardized transvaginal grayscale and Doppler ultrasound examination by an experienced ultrasound examiner using a high-end ultrasound system. Clinical and sonographic data were entered into a web-based protocol. We assessed how strongly sonographic characteristics, according to IETA, were associated to outcome at hysterectomy, i.e. tumor stage, grade, and histological type. After excluding 176 women (no or delayed hysterectomy, final diagnosis other than endometrial cancer, or incomplete data), 1538 women were included in our statistical analysis. Median age was 65 years (range 27-98), and median BMI 28.4 (range 16-67), 1378 (89.7%) women were postmenopausal, and 1296 (84.2%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage. High-risk tumors (stage 1A, grade 3 or non-endometrioid or ≥ stage 1B) were less likely to have regular endometrial myometrial border (difference of -23%, 95% CI -27 to -18%), whilst they were larger (mean endometrial thickness; difference of +9 mm, 95% CI +8 to +11 mm), more frequently had non-uniform echogenicity (difference of +10%, 95% CI +5 to +15%), a multiple, multifocal vessel pattern (difference of +21%, 95% CI +16 to +26%), and a moderate or high color score (difference of +22%, 95% CI +18 to +27%), than low-risk tumors. Grayscale and color Doppler ultrasound features are associated with grade and stage, and differ between high and low risk endometrial cancer. This article is protected by copyright. All rights reserved.

  12. Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.

    Science.gov (United States)

    Carrarelli, Patrizia; Funghi, Lucia; Ciarmela, Pasquapina; Centini, Gabriele; Reis, Fernando M; Dela Cruz, Cynthia; Mattei, Alberto; Vannuccini, Silvia; Petraglia, Felice

    2017-12-01

    Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.

  13. Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

    Science.gov (United States)

    Obón-Santacana, M; Kaaks, R; Slimani, N; Lujan-Barroso, L; Freisling, H; Ferrari, P; Dossus, L; Chabbert-Buffet, N; Baglietto, L; Fortner, R T; Boeing, H; Tjønneland, A; Olsen, A; Overvad, K; Menéndez, V; Molina-Montes, E; Larrañaga, N; Chirlaque, M-D; Ardanaz, E; Khaw, K-T; Wareham, N; Travis, R C; Lu, Y; Merritt, M A; Trichopoulou, A; Benetou, V; Trichopoulos, D; Saieva, C; Sieri, S; Tumino, R; Sacerdote, C; Galasso, R; Bueno-de-Mesquita, H B; Wirfält, E; Ericson, U; Idahl, A; Ohlson, N; Skeie, G; Gram, I T; Weiderpass, E; Onland-Moret, N C; Riboli, E; Duell, E J

    2014-01-01

    Background: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. Methods: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. Results: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). Conclusions: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers. PMID:24937665

  14. Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development.

    Directory of Open Access Journals (Sweden)

    Allison Jones

    2013-11-01

    Full Text Available Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development.Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64 and control samples (n = 23 revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A. Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop

  15. Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development

    Science.gov (United States)

    Hayward, Jane D.; Kannan, Athilakshmi; Mould, Tim; West, James; Zikan, Michal; Cibula, David; Fiegl, Heidi; Lee, Shih-Han; Wik, Elisabeth; Hadwin, Richard; Arora, Rupali; Lemech, Charlotte; Turunen, Henna; Pakarinen, Päivi; Jacobs, Ian J.; Salvesen, Helga B.; Bagchi, Milan K.; Bagchi, Indrani C.; Widschwendter, Martin

    2013-01-01

    Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to

  16. High Frequency of RPL22 Mutations in Microsatellite-Unstable Colorectal and Endometrial Tumors

    NARCIS (Netherlands)

    Monteira Ferreira, Ana M.; Tuominen, Iina; van Dijk-Bos, Krista; Sanjabi, Bahram; van der Sluis, Tineke; van der Zee, Ate G.; Hollema, Harry; Zazula, Monika; Sijmons, Rolf H.; Aaltonen, Lauri A.; Westers, Helga; Hofstra, Robert M. W.

    2014-01-01

    Ribosomal Protein L22 (RPL22) encodes a protein that is a component of the 60S subunit of the ribosome. Variants in this gene have recently been linked to cancer development. Mutations in an A8 repeat in exon 2 were found in a recent study in 52% of microsatellite-unstable endometrial tumors. These

  17. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

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    Devic Ana

    2015-12-01

    Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.

  18. Reduction in neural activation to high-calorie food cues in obese endometrial cancer survivors after a behavioral lifestyle intervention: a pilot study

    Directory of Open Access Journals (Sweden)

    Nock Nora L

    2012-06-01

    Full Text Available Abstract Background Obesity increases the risk of endometrial cancer (EC and obese EC patients have the highest risk of death among all obesity-associated cancers. However, only two lifestyle interventions targeting this high-risk population have been conducted. In one trial, food disinhibition, as determined by the Three-Factor Eating Questionnaire, decreased post-intervention compared to baseline, suggesting an increase in emotional eating and, potentially, an increase in food related reward. Therefore, we evaluated appetitive behavior using functional magnetic resonance imaging (fMRI and a visual food task in 8 obese, Stage I/II EC patients before and after a lifestyle intervention (Survivors in Uterine Cancer Empowered by Exercise and a Healthy Diet, SUCCEED, which aimed to improve nutritional and exercise behaviors over 16 group sessions in 6 months using social cognitive theory. Results Congruent to findings in the general obese population, we found that obese EC patients, at baseline, had increased activation in response to high- vs. low-calorie food cues after eating a meal in brain regions associated with food reward (insula, cingulate gyrus; precentral gyrus; whole brain cluster corrected, p  Conclusions Our preliminary results suggest behavioral lifestyle interventions may help to reduce high-calorie food reward in obese EC survivors who are at a high-risk of death. To our knowledge, this is the first study to demonstrate such changes.

  19. Prognostic Evaluation of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Endometrial Cancer

    DEFF Research Database (Denmark)

    Vilstrup, Mie Holm; Jochumsen, Kirsten M; Hess, Søren

    2017-01-01

    OBJECTIVE: This study aims to ascertain if semiquantitative measurements derived from F-fluorodeoxyglucose positron emission tomography/computed tomography can be used as prognostic markers in patients with newly diagnosed endometrial cancer. MATERIALS AND METHODS: Patients with endometrial cancer...... proportional regression models were used for prognostic evaluation. RESULTS: Eighty-three patients (median age, 69.9 y; range, 26.8-91.1) with primarily high-risk endometrial cancer or suspected high The International Federation of Gynecology and Obstetrics stage were included. Mean follow-up time was 3......-risk endometrial cancer. Thus, SUVmax and cTLG might help identify patients who could benefit from a more aggressive treatment strategy or closer surveillance....

  20. Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies

    Science.gov (United States)

    Pfeiffer, Ruth M.; Park, Yikyung; Kreimer, Aimée R.; Lacey, James V.; Pee, David; Greenlee, Robert T.; Buys, Saundra S.; Hollenbeck, Albert; Rosner, Bernard; Gail, Mitchell H.; Hartge, Patricia

    2013-01-01

    Background Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer. Methods and Findings Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively. Conclusions These models predict absolute risks for breast, endometrial, and

  1. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies.

    Directory of Open Access Journals (Sweden)

    Ruth M Pfeiffer

    Full Text Available Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP], we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI; the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04 for breast cancer and 1.08 (95% CI: 0.97-1.19 for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29. The areas under the receiver operating characteristic curves (AUCs; discriminatory power were 0.58 (95% CI: 0.57-0.59, 0.59 (95% CI: 0.56-0.63, and 0.68 (95% CI: 0.66-0.70 for the breast, ovarian, and endometrial models, respectively.These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may

  2. LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

    Science.gov (United States)

    Noci, Ivo; Sorbi, Flavia; Mannini, Luca; Projetto, Elisabetta; Pillozzi, Serena; Ghizzoni, Viola; Lottini, Tiziano; Moncini, Daniela; Baroni, Gianna; Mungai, Francesco; Arcangeli, Annarosa; Fambrini, Massimiliano

    2016-01-01

    A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

  3. Abdominal obesity and endometrial cancer in egyptian females with postmenopausal bleeding.

    Science.gov (United States)

    Zaki, Adel; Gaber, Afaf; Ghanem, Ebrahim; Moemen, Maha; Shehata, Gihan

    2011-11-01

    Endometrial cancer is the most common type of female genital tract malignancies. We intended to assess the relation between different measures of obesity and the risk to develop endometrial cancer in Egyptian females with postmenopausal bleeding (PMB). The study was conducted in Alexandria, Egypt and included all postmenopausal females presenting to the University Hospital of Gynecology and Obstetrics with PMB within the study period (from January 1 to September 30). A questionnaire was completed, and data about anthropometric measurements including weight, height, and waist circumference were collected. Vaginal sonography, dilatation and curettage, and pathological examination were done by experts for all participants. Endometrial cancer was diagnosed in 38% of females presenting with PMB. Using ROC curve analysis, only the measure of abdominal obesity (waist circumference) showed significant accuracy in predicting endometrial cancer (area = 0.63, P obesity (W/H ratio) showed border line significant relation (OR = 2, 95% CI 1-4.1), whereas waist circumference (≥88 vs. ≤88 cm) showed strikingly high OR (OR = 13.6, 95%CI 4-46.6). The risk of abdominal obesity on endometrial cancer remains very high (OR = 15.8, 95%CI 4.1-60.9) even after adjustment, in a logistic model, for other risk factors such as age at presentation, age at menarche, age at menopause, family history of malignancy, and gravidity. Abdominal obesity (waist circumference >88 cm) is the best measure of obesity to be used in predicting the risk of endometrial cancer in Egyptian females with PMB.

  4. Adjuvant radiotherapy for stage I endometrial cancer

    Science.gov (United States)

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. Objectives To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. Selection criteria We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Data collection and analysis Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. Main results We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes. EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2

  5. [Endometrial cancer: Predictive models and clinical impact].

    Science.gov (United States)

    Bendifallah, Sofiane; Ballester, Marcos; Daraï, Emile

    2017-12-01

    In France, in 2015, endometrial cancer (CE) is the first gynecological cancer in terms of incidence and the fourth cause of cancer of the woman. About 8151 new cases and nearly 2179 deaths have been reported. Treatments (surgery, external radiotherapy, brachytherapy and chemotherapy) are currently delivered on the basis of an estimation of the recurrence risk, an estimation of lymph node metastasis or an estimate of survival probability. This risk is determined on the basis of prognostic factors (clinical, histological, imaging, biological) taken alone or grouped together in the form of classification systems, which are currently insufficient to account for the evolutionary and prognostic heterogeneity of endometrial cancer. For endometrial cancer, the concept of mathematical modeling and its application to prediction have developed in recent years. These biomathematical tools have opened a new era of care oriented towards the promotion of targeted therapies and personalized treatments. Many predictive models have been published to estimate the risk of recurrence and lymph node metastasis, but a tiny fraction of them is sufficiently relevant and of clinical utility. The optimization tracks are multiple and varied, suggesting the possibility in the near future of a place for these mathematical models. The development of high-throughput genomics is likely to offer a more detailed molecular characterization of the disease and its heterogeneity. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  6. Adiponectin and Endometrial Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Fangxin Zeng

    2015-07-01

    Full Text Available Objective: This study evaluates the association between serum adiponectin concentrations and the risk of endometrial cancer through a comprehensive meta-analysis of currently available clinical data. Methods: PubMed, Embase, the Chinese Biomedical Literature Database and the Science Citation Index (ISI Web of Science were searched for studies that examined the association between blood adiponectin concentrations and the risk of endometrial cancer. Data from studies that met the inclusion criteria were systematically reviewed, and pooled analyses were performed according to the guidelines of Meta-Analysis of Observational Studies in Epidemiology and PRIMSA. Results: Eight case-control studies (including 1257 endometrial cancer patients and 2008 controls and four nested case-control studies (including 659 endometrial cancer patients and 1398 controls were included. We found that serum adiponectin level was inversely correlated with the risk of endometrial cancer development after pooling the case-control studies (OR = 0.50, 95% CI: 0.39-0.60; P P=0.060, particularly in postmenopausal women without current hormone replacement therapy (OR = 0.62, 95% CI: 0.44-0.86; P = 0.004. Conclusions: Meta-analysis of currently available clinical evidence supports the association between high serum adiponectin concentration and reduced risk of endometrial cancer development, particularly in the group of postmenopausal women without current hormone replacement therapy. However, additional studies with prospective design are required to fully support this linkage.

  7. Determination of Prognostic Factors for Vaginal Mucosal Toxicity Associated With Intravaginal High-Dose Rate Brachytherapy in Patients With Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bahng, Agnes Y.; Dagan, Avner [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Bruner, Deborah W. [University of Pennsylvania School of Nursing, Philadelphia, PA (United States); Lin, Lilie L., E-mail: lin@xrt.upenn.edu [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    2012-02-01

    Purpose: The objective of this study was to determine the patient- and treatment-related prognostic factors associated with vaginal toxicity in patients who received intravaginal high dose rate (HDR) brachytherapy alone as adjuvant treatment for endometrial cancer. Secondary goals of this study included a quantitative assessment of optimal dilator use frequency and a crude assessment of clinical predictors for compliant dilator use. Methods and Materials: We retrospectively reviewed the charts of 100 patients with histologically confirmed endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection and adjuvant intravaginal brachytherapy between 1995 and 2009 at the Hospital of University of Pennsylvania. The most common treatment regimen used was 21 Gy in three fractions (71 patients). Symptoms of vaginal mucosal toxicity were taken from the history and physical exams noted in the patients' charts and were graded according to the Common Toxicity Criteria for Adverse Events v. 4.02. Results: The incidence of Grade 1 or asymptomatic vaginal toxicity was 33% and Grade 2-3 or symptomatic vaginal toxicity was 14%. Multivariate analysis of age, active length, and dilator use two to three times a week revealed odds ratios of 0.93 (p = 0.013), 3.96 (p = 0.008), and 0.17 (p = 0.032) respectively. Conclusion: Increasing age, vaginal dilator use of at least two to three times a week, and shorter active length were found to be significantly associated with a decreased risk of vaginal stenosis. Future prospective studies are necessary to validate our findings.

  8. Physical activity, sedentary behavior, and endometrial cancer risk in the NIH-AARP Diet and Health Study

    National Research Council Canada - National Science Library

    Gierach, Gretchen L; Chang, Shih-Chen; Brinton, Louise A; Lacey, Jr, James V; Hollenbeck, Albert R; Schatzkin, Arthur; Leitzmann, Michael F

    2009-01-01

    .... We examined relationships of activity patterns with endometrial cancer incidence in the NIH-AARP Diet and Health Study cohort, which included 109,621 women, ages 50-71, without cancer history, who...

  9. Theories of endometrial carcinogenesis: a multidisciplinary approach.

    Science.gov (United States)

    Sherman, M E

    2000-03-01

    Historical observations have suggested that endometrial carcinomas vary in histopathologic appearance and clinical features. More recent, systematic studies have provided epidemiologic, clinicopathologic, and molecular support for these observations. Specifically, studies suggest that the most common type of endometrial carcinoma, endometrioid adenocarcinoma, develops from endometrial hyperplasia in the setting of excess estrogen exposure and usually pursues an indolent clinical course. In contrast, a minority of endometrial carcinomas, best represented by serous carcinoma, do not seem to be related to estrogenic risk factors or elevated serum hormone levels, and these tumors seem to develop from atrophic rather than hyperplastic epithelium. We have proposed that serous carcinomas develop from "endometrial intraepithelial carcinoma," a lesion representing malignant transformation of the endometrial surface epithelium. Whereas endometrioid carcinoma and endometrial hyperplasia are associated with microsatellite instability and ras and PTEN mutations, serous carcinoma and endometrial intraepithelial carcinoma are associated with p53 mutations and abnormal accumulation of p53 protein. Based on these data regarding the pathogenesis of endometrioid and serous carcinoma, we have proposed a dualistic model of endometrial carcinogenesis incorporating a "classic" estrogen-driven pathway and an "alternative" pathway seemingly unrelated to hormones. It is hoped that further studies may permit the extension and modification of this model and that these advances will lead to improved diagnosis, management, and prevention.

  10. Estrogen replacement therapy after endometrial cancer: a survey of physicians' prescribing practice.

    Science.gov (United States)

    Hancke, K; Foeldi, M; Zahradnik, H P; Gitsch, G; Gilbert, L; Denschlag, D

    2010-06-01

    To determine whether the prescribing practice of physicians with regard to estrogen replacement therapy (ERT) in symptomatic women with previous endometrial cancer is consistent with the available evidence. A descriptive survey was conducted among physicians in Germany, using a questionnaire containing two hypothetical cases of endometrial cancer patients ('low-risk' and 'high-risk' disease) and menopausal symptoms. Physicians were asked about their prescribing practice concerning moderate to severe menopausal symptoms. Four hundred and twenty questionnaires were sent out, with an overall response rate of 39.8%; 45.6% in the 'low-risk' case and 75.4% in the 'high-risk' case (p alternatives (44.8% phytoestrogens, 29.0% selective serotonin reuptake inhibitors). Despite the evidence that ERT does not increase the risk of recurrence of endometrial cancer, many physicians are reluctant to prescribe ERT in women suffering from moderate to severe menopausal symptoms.

  11. Awareness of the association between obesity and peri-operative risk among newly diagnosed patients with complex atypical hyperplasia and endometrial cancer.

    Science.gov (United States)

    Kuroki, Lindsay M; Benn, Teri E; Dukes, Jonathan L; Hagemann, Andrea R; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Massad, L Stewart; Zighelboim, Israel

    2015-04-01

    To evaluate knowledge of obesity-related peri-operative risks in with women newly diagnosed complex atypical hyperplasia and endometrial cancer. Cross sectional study of patients newly diagnosed with complex atypical hyperplasia or endometrial cancer who underwent preoperative counseling between 2011 and 2014, using a 17-item questionnaire. Obesity was defined as body mass index (BMI) of 30 kg/m2 or greater. Bivariate analysis was conducted using Pearson's Chi-Square or Fisher's Exact tests where appropriate and Mann-Whitney U for continuous variables. Of 98 patients recruited, mean age was 58 years, 87% were obese, 83% white, and 51% had grade 1 endometrioid adenocarcinomas. Sixty-four percent of obese women reported that their physicians had discussed surgical risks related to obesity. However, 17% of obese and 42% of non-obese patients responded that they were unsure of the peri-operative risks associated with obesity. There was substantial lack of understanding among obese patients regarding their increased risks of respiratory problems (29%), thromboembolism (29%), heart attack (35%), or longer operating time (35%) and hospital stay (47%). However, obese patients were more aware of wound infection risks associated with obesity compared to their non-obese counterparts (72% vs. 31%, p=0.004). Pre-operative counseling for obese women with newly diagnosed endometrial cancer should incorporate more focused education about obesity-related risks. They report being knowledgeable about the risks associated with their surgery, however, more than a quarter are unaware of the impact obesity has on respiratory problems, thromboembolism, wound infection, heart attack or longer operating time and hospital stay.

  12. Disseminated tumor cells are not associated with established risk factors, L1CAM immunoreactivity and outcome in endometrial carcinoma.

    Science.gov (United States)

    Kommoss, Stefan; Hartkopf, Andreas D; Krämer, Bernhard; Bunz, Anne-Kathrin; Grevenkamp, Friederike; Kommoss, Felix; Pasternak, Jana; Arbabi, Sabine M; Wallwiener, Markus; Staebler, Annette; Lax, Sigurd F; Brucker, Sara Y; Taran, Florin-Andrei

    2017-11-01

    The presence of disseminated tumor cells (DTC) in the bone marrow of endometrial carcinoma patients has been demonstrated previously. In contrast to breast cancer, no prognostic significance or association with clinicopathological features was revealed for endometrial carcinoma so far. The aim of this study was to investigate DTC in a large patient cohort with in-depth pathology review data available and to study DTC occurrence in the context of L1CAM and long-term disease specific follow-up. Patients treated for endometrial carcinoma at the Tuebingen University Women's hospital between 2003 and 2013 were identified. Cases with previous expert central pathology review including L1CAM immunohistochemistry and bone marrow aspirates available were selected. The presence of DTC and L1CAM expression was studied immunohistochemically. In 395 cases with a confirmed diagnosis of endometrial carcinoma, bone marrow aspirates were available. DTC were detected in 17.2%. The presence of DTC was independent from tumor histology, grade, lymphovascular space involvement (LVSI), FIGO stage, myoinvasion, L1CAM immunoreactivity, and nodal metastasis. DTC occurred less frequently in cases with a microcystic elongated and fragmented (MELF) pattern of invasion (2.2 vs. 21.8%, p = 0.0003). Disease progression was distributed equally among patients with and without DTC present. We were able to confirm previous findings of DTC presence in a large well-characterized cohort of endometrial carcinoma patients. DTC are detectable in almost one-fifth of endometrial carcinoma and occur less frequently with a MELF pattern of invasion. Further studies investigating the role of DTC in endometrial carcinoma are warranted.

  13. Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting: taking endometrial cancer trials into the translational era.

    Science.gov (United States)

    Creutzberg, Carien L; Kitchener, Henry C; Birrer, Michael J; Landoni, Fabio; Lu, Karen H; Powell, Melanie; Aghajanian, Carol; Edmondson, Richard; Goodfellow, Paul J; Quinn, Michael; Salvesen, Helga B; Thomas, Gillian

    2013-10-01

    The second Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting was held on December 1, 2012, and included international multidisciplinary representatives of the 24 member groups. The aims were to review recent advances in molecular pathology of endometrial cancer, focusing on molecular-based therapy, and to identify key hypotheses and issues to be addressed through international collaborative clinical trials. Reviews and summaries of current knowledge were presented followed by parallel working group sessions for surgery, adjuvant and systemic therapy, and translational research. Plenary discussions were held to integrate translational and clinical issues, and a final discussion session to agree on key trial concepts. Proposals to take forward on the following trials were agreed: (1) lymphadenectomy to direct adjuvant treatment in women with high-risk endometrial cancer, including a sentinel node substudy; (2) conservative therapy for low-risk endometrial cancers in morbidly obese women with high surgical risks and for fertility-sparing treatment in premenopausal patients; (3) adjuvant therapy for women with early-stage carcinosarcoma. A proposal was made that a GCIG Early Phase Consortium be developed to serve as an international platform for rapid assessment of biomarkers.

  14. Long-term, adverse genitourinary outcomes among endometrial cancer survivors in a large, population-based cohort study.

    Science.gov (United States)

    Soisson, Sean; Ganz, Patricia A; Gaffney, David; Rowe, Kerry; Snyder, John; Wan, Yuan; Deshmukh, Vikrant; Newman, Mike; Fraser, Alison; Smith, Ken; Herget, Kimberly; Hanson, Heidi A; Wu, Yelena P; Stanford, Joseph; Werner, Theresa L; Setiawan, Veronica Wendy; Hashibe, Mia

    2017-12-27

    With the increasing incidence of endometrial cancer, the high survival rate, and the large number of endometrial cancer survivors, investigations of long-term genitourinary outcomes are important for the management of these outcomes among endometrial cancer survivors. Cohorts of 2648 endometrial cancer survivors diagnosed in the state of Utah between 1997 and 2012 and 10,503 general population women were identified. All ICD-9 diagnosis codes were collected from the state's two largest healthcare systems and statewide databases. Multivariate Cox regression models were used to estimate hazard ratios at 1-5years and >5-10years after endometrial cancer diagnosis for genitourinary outcomes. Endometrial cancer survivors were at elevated risk for urinary system disorders between 1 and 5years (HR: 1.64, 95% CI: 1.50-1.78) and >5-10years (HR: 1.40, 95% CI: 1.26-1.56) and genital organ disorders between 1 and 5years (HR: 1.71, 95% CI: 1.58-2.03) and >5-10years (HR: 1.33, 95% CI: 1.19-1.49). Significantly elevated risk was observed among endometrial cancer survivors for renal failure, chronic kidney disease, urinary tract infections, and nonmalignant breast conditions, persisting between >5-10years. Between 1 and 5years after cancer diagnosis, those with higher stage, higher grade, older age and treated with radiation or chemotherapy were at higher risk for urinary disorders. Endometrial cancer survivors were at higher risk for many genitourinary outcomes compared to women from the general population. This study presents evidence suggesting the necessity of increased monitoring and counseling for genitourinary disorders for endometrial cancer patients both immediately after treatment cessation and for years afterwards. Copyright © 2017. Published by Elsevier Inc.

  15. Vitamin D and calcium intake in relation to risk of endometrial cancer: a systematic review of the literature.

    Science.gov (United States)

    McCullough, Marjorie L; Bandera, Elisa V; Moore, Dirk F; Kushi, Lawrence H

    2008-04-01

    In response to a recent ecologic study of UV exposure and endometrial cancer incidence, we present the epidemiologic evidence on the relation between intake of vitamin D and its metabolically related nutrient, calcium, and the occurrence of endometrial cancer. We conducted a systematic literature review and meta-analysis of vitamin D and calcium in relation to endometrial cancer, including peer-reviewed manuscripts published up to May 2007. Random and fixed effects summary estimates were computed. Pooled analyses of the three case-control studies of dietary vitamin D and endometrial cancer uncovered heterogeneous results that were not significant in random or fixed effects analyses. Cut-points for the highest vitamin D intakes ranged from >244 to >476 IU/day. Qualitatively similar findings were observed for dietary calcium. Only two studies provided estimates for calcium supplements (random effects OR=0.62, 95% CI 0.39-0.99; fixed effects OR=0.62, 95% CI 0.42-0.93, for top vs. bottom category, p for heterogeneity=0.25). The limited epidemiological evidence suggests no relation between endometrial cancer in the ranges of dietary vitamin D examined, and suggests a possible inverse association for calcium from supplements. Prospective studies, ideally including plasma 25(OH) D to estimate vitamin D input from diet and sun exposure, are needed to further explore these hypotheses.

  16. Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis.

    Science.gov (United States)

    Bregar, Amy J; Alejandro Rauh-Hain, J; Spencer, Ryan; Clemmer, Joel T; Schorge, John O; Rice, Laurel W; Del Carmen, Marcela G

    2017-04-01

    To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p<0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p<0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p<0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16-1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80-0.93). Among women with high-grade endometrial cancer, African American women have lower all-cause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The centralization of robotic surgery in high-volume centers for endometrial cancer patients--a study of 6560 cases in the U.S.

    Science.gov (United States)

    Chan, John K; Gardner, Austin B; Taylor, Katie; Blansit, Kevin; Thompson, Caroline A; Brooks, Rebecca; Yu, Xinhua; Kapp, Daniel S

    2015-07-01

    To evaluate the hospital and patient factors associated with robotic surgery for endometrial cancer in the United States. Data was obtained from the Nationwide Inpatient Sample from the year 2010. Chi-squared and multivariate analyses were used for statistical analysis. Of the 6560 endometrial cancer patients who underwent surgery, the median age was 62 (range: 22 to 99). 1647 (25%) underwent robotic surgery, 820 (13%) laparoscopic, and 4093 (62%) had open surgery. The majority was White (65%). Hospitals with 76 or more hysterectomy cases for endometrial cancer patients per year (4% of hospitals in the study) performed 31% of all hysterectomies and 40% of all robotic hysterectomies (probotic surgery compared to 15% of Hispanics, 12% of Blacks, and 11% of Asians (probotic surgery more than patients with low or middle incomes (probotic surgery compared to only 14% of Medicaid patients and 12% of uninsured patients (probotic surgeries for endometrial cancer were performed at a small number of high-volume hospitals in the United States. Socioeconomic status, insurance type, and race were also important predictors for the use of RS. Further studies are warranted to better understand the barriers to receiving minimally invasive surgery. Copyright © 2015. Published by Elsevier Inc.

  18. MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration

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    Liu Ping

    2011-03-01

    Full Text Available Abstract Background To determine the effect of higher progesterone (P level on endometrial receptivity. Methods This was a prospective analysis conducted in the Reproductive Medical Center of Peking University Third Hospital. All patients received IVF treatment and canceled embryo transfer in the same cycle and were divided into group 1 (normal P; 7 patients and group 2 (elevated P; 12 patients. Endometrial biopsies were performed 6 days after oocyte retrieval. The global miRNA and mRNA gene expressions in endometrial biopsies were investigated with a V4.0 miRNA probe and 22 K Human Genome Array. Fold ratios were derived to compare gene regulation between the groups. Spp1 and Ang gene expression was selected to verify the array results by RT-PCR and the protein expression of osteopontin and VEGF was determined using an immunohistochemical method. Results There were 4 miRNA (all down-regulated and 22 mRNA (13 up-regulated and 9 down-regulated exhibiting differential expression between the groups on the microRNA and microarray chips. miRNA-451, Spp1, and Ang expression in RT-PCR verified the array results. Osteopontin and VEGF were also shown to have positive expression in the endometrium. Conclusions Data from microRNA and microarray analysis suggests dissimilar endometrial receptivity in patients with high P levels on the day of hCG, and elevated osteopontin and decreased VEGF had poor pregnancy rates.

  19. Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies.

    Science.gov (United States)

    Keum, NaNa; Ju, Woong; Lee, Dong Hoon; Ding, Eric L; Hsieh, Chung C; Goodman, Julie E; Giovannucci, Edward L

    2014-08-01

    Although considerable evidence suggests that leisure-time physical activity is associated with a reduced risk of endometrial cancer (EC), the shape of dose-response relationship has not been investigated and previous meta-analyses have not accounted for differences in measures of physical activity. To address such issues, we conducted linear and nonlinear dose-response meta-analyses by metabolic equivalent of task (MET)-hour/week and hour/week, respectively, based on observational studies published up to September 2013 identified from PubMed and Embase databases. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. In the linear dose-response analysis, an increase in leisure-time physical activity by 3 MET-hour/week was associated with an ∼2% reduced risk of EC (summary RR = 0.98, p = 0.02, 95% CI = 0.95-1.00, I(2)  = 53%, p(heterogeneity)  = 0.06, three case-control studies and three cohort studies, 3,460 cases, range of activity = 0-50 MET-hour/week) and an increase by an hour/week was associated with an ∼5% reduced risk of EC (summary RR = 0.95, p response meta-analysis suggested that the curve may plateau at 10 MET-hour/week (p(change) in slope  = 0.04) but this statistical significance was sensitive to one study. No evidence of a nonlinear association was indicated by hour/week (p(change) in slope  > 0.69). In conclusion, an increase in leisure-time physical activity may continue to decrease EC risk, within the range of 0-50 MET-hour/week or 0-15 hour/week. Future studies should evaluate possible independent role of intensity of physical activity and effect modification by obesity. © 2013 UICC.

  20. Hysteroscopic findings of endometrial carcinoma. Evaluation of 104 cases.

    Science.gov (United States)

    Triolo, O; Antico, F; Palmara, V; Benedetto, V; Panama, S; Nicotina, P A

    2005-01-01

    Retrospective evaluation of hysteroscopic findings in the accurate diagnosis of endometrial carcinoma. A retrospective monocentric study from January 1995 to December 2004. One hundred and four patients with hysteroscopic aspects evocative of endometrial carcinoma confirmed by endometrial biopsy during diagnostic hysteroscopy, by surgical hysteroscopic resection pieces or by hysterectomy specimen were included. Among the 104 patients, diagnostic hysteroscopy pointed out endometrial features suggestive of endometrial carcinoma in 102 cases. In two women diagnostic hysteroscopy failed to diagnose endometrial malignancy which was identified on pieces of polyps by surgical hysteroscopic resection. Polypoid proliferations cerebroid in appearance, with ulceration and necrosis, friable and with irregular vessels, represent endometrial findings highly indicative of malignancy. The diagnosis may be missed in cases of focal neoplasias, within endometrial polyps or in conditions of unsatisfactory endouterine visualization.

  1. High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells

    Science.gov (United States)

    Khanaki, Korosh; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Darabi, Masoud; Mehdizadeh, Amir; Shabani, Mahdi; Rahimipour, Ali; Nouri, Mohammad

    2014-01-01

    Background: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. Objective: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. Materials and Methods: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. Results: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). Conclusion: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis. PMID:25709631

  2. Bokhman Redux: Endometrial cancer "types" in the 21st century.

    Science.gov (United States)

    Suarez, Adrian A; Felix, Ashley S; Cohn, David E

    2017-02-01

    In 1983 Jan V. Bokhman, M.D. published a landmark paper entitled "Two Pathogenetic Types of Endometrial Carcinoma" in which an enduring dualistic view of endometrial cancer was first proposed. "Type I" cancers are thought to represent estrogen driven mostly low grade endometrioid tumors strongly associated with obesity and other components of the metabolic syndrome. "Type II" cancers represent higher grade non-endometrioid tumors for which the latter associations are less significant. Basic tenets of this dichotomy including significant prognostic differences have been abundantly confirmed by later literature. The construct has in turn contributed a useful framework for decades of teaching and scientific advancement across disciplines. However, recent large epidemiologic studies indicate a more complex web of risk factors with obesity and hormones likely playing an important role across the entire endometrial cancer histologic and clinical spectrum. Moreover, high quality molecular data and refinements in pathologic classification challenge any simplistic classification of endometrial cancer. For example, the Cancer Genome Atlas (TCGA) recently defined four clinically distinct endometrial cancer types based on their overall mutational burden, specific p53, POLE and PTEN mutations, microsatellite instability and histology. Additionally, new histologic categories with clear prognostic implications have been accepted and it is becoming evident from an epidemiologic point of view that metabolic factors may play an important role in endometrial cancer overall. While Bokhman's intuitive dualistic model remains relevant when working with large registries and databases lacking granular information; most other efforts should integrate clinical, pathological and molecular specifics into more nuanced classifications. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Dietary Vitamin D Exposure Prevents Obesity-induced Increase in Endometrial Cancer in Pten+/− Mice

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    Yu, Wei; Cline, Mark; Maxwell, Larry G.; Berrigan, David; Rodriguez, Gustavo; Warri, Anni; Hilakivi-Clarke, Leena

    2010-01-01

    The possibility that dietary VD3 exposure inhibits endometrial carcinogenesis in an animal model, and modifies the enhanced risk of endometrial carcinoma associated with obesity was investigated. When 4 weeks of age, Pten+/− and wildtype mice were each divided into four treatment groups and fed AIN93G control diet, or AIN93G based diet containing either 25K IU of VD3/kg diet, 58% fat to induce obesity (high fat), or high fat and 25K IU of VD3/kg diet. Mice were kept on these diets until they were sacrificed at week 28. Although VD3 did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial lesions. Specifically, high fat diet increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet fed Pten+/− mice to 78% in obese mice. Dietary VD3 decreased the incidence of endometrial pathology in obese Pten+/− mice to 25% (pendometrial expression of 25-hydroxylase (25-OHase), 1α-OHase and vitamin D receptor in the wildtype and Pten+/− mice. Estrogen receptor (ER) -α mRNA levels were higher (pobesity induced increase in osteopontin (pobese in Pten+/− mice. Our data confirm the known association between obesity and endometrial cancer risk. Dietary exposure to VD3 inhibited the carcinogenic effect of obesity on the endometrium; this protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin. PMID:20858763

  4. Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- mice.

    Science.gov (United States)

    Yu, Wei; Cline, Mark; Maxwell, Larry G; Berrigan, David; Rodriguez, Gustavo; Warri, Anni; Hilakivi-Clarke, Leena

    2010-10-01

    The possibility that dietary vitamin D(3) (VD(3)) exposure inhibits endometrial carcinogenesis in an animal model and modifies the enhanced risk of endometrial carcinoma associated with obesity was investigated. At 4 weeks of age, Pten(+/-) and wild-type mice were each divided into four treatment groups and fed AIN93G control diet, or AIN93G-based diet containing either 25,000 international units of VD(3) per kilogram of diet, 58% fat to induce obesity (high fat), or high fat and 25,000 international units of VD(3) per kilogram of diet. Mice were kept on these diets until they were sacrificed at week 28. Although VD(3) did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial lesions. Specifically, high-fat diet increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet-fed Pten(+/-) mice to 78% in obese mice. Dietary VD(3) decreased the incidence of endometrial pathology in obese Pten(+/-) mice to 25% (P endometrial expression of 25-hydroxylase, 1α-hydroxylase, and vitamin D receptor in the wild-type and Pten(+/-) mice. Estrogen receptor-α mRNA levels were higher (P obesity-induced increase in osteopontin (P obese Pten(+/-) mice. Our data confirm the known association between obesity and endometrial cancer risk. Dietary exposure to VD(3) inhibited the carcinogenic effect of obesity on the endometrium. This protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin. ©2010 AACR.

  5. Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos.

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    Charlotte H E Weimar

    Full Text Available BACKGROUND: The aetiology of recurrent miscarriage (RM remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. METHODOLOGY/PRINCIPAL FINDINGS: Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13, a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12 or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05 and compared to the migration in the presence of high-quality embryo (p<0.01. Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001. CONCLUSIONS: H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM.

  6. Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia

    Science.gov (United States)

    Kadirogullari, Pinar; Atalay, Cemal Resat; Sari, Mustafa Erkan

    2015-01-01

    evaluated as stage 3C. Conclusion The risk of endometrial cancer in patients diagnosed with endometrial hyperplasia especially endometrial hyperplasia ranges between 15% to 45% and among them 7.9%–51% are found to have myometrial inversion. Therefore, preoperative ultrasound and magnetic resonance imaging should be perfomed in patients diagnosed with complex atypical hyperplasia. Even intraoperative frozen section examination can provide useful information in selected cases. PMID:26557570

  7. Late-onset endometrial ablation failure

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    Morris Wortman

    2017-07-01

    While the short term safety and efficacy of these devices has been reported in numerous clinical trials we only recently are becoming aware of the high incidence of late-onset endometrial ablation failures (LOEAFs associated with these procedures. Currently, about a quarter of women who undergo a GEA procedure will eventually require a hysterectomy while an unknown number have less than satisfactory results. In order to reduce these suboptimal outcomes physicians must better understand the etiology and risk factors that predispose a patient toward the development of LOEAF as well as current knowledge of patient and procedure selection for EA as well as treatment options for these delayed complications.

  8. The association between polycystic ovary syndrome and endometrial cancer.

    OpenAIRE

    Chedumbarum Pillay, O. D.

    2010-01-01

    HYPOTHESIS: Women suffering from polycystic ovary syndrome have an increased risk of developing endometrial carcinoma. AIM: To determine whether people with polycystic ovary syndrome have an increased risk of developing endometrial carcinoma. BACKGROUND: Endometrial cancer is one of the commonest cancers to occur in women in the Western World and unopposed oestrogen stimulation of the uterus is amongst one of the aetiologies postulated for this condition. It is generally assumed that ...

  9. Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

    Science.gov (United States)

    Ip, Philip Pun-Ching

    2018-02-14

    Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.

  10. Evaluation of endometrial cancer epidemiology in Romania.

    Science.gov (United States)

    Bohîlțea, R E; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, L C

    2015-01-01

    Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women's genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data.

  11. Contemporary Clinical Management of Endometrial Cancer

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    Helen E. Dinkelspiel

    2013-01-01

    Full Text Available Although the contemporary management of endometrial cancer is straightforward in many ways, novel data has emerged over the past decade that has altered the clinical standards of care while generating new controversies that will require further investigation. Fortunately most cases are diagnosed at early stages, but high-risk histologies and poorly differentiated tumors have high metastatic potential with a significantly worse prognosis. Initial management typically requires surgery, but the role and extent of lymphadenectomy are debated especially with well-differentiated tumors. With the changes in surgical staging, prognosis correlates more closely with stage, and the importance of cytology has been questioned and is under evaluation. The roles of radiation in intermediate-risk patients and chemotherapy in high-risk patients are emerging. The therapeutic index of brachytherapy needs to be considered, and the best sequencing of combined modalities needs to balance efficacy and toxicities. Additionally novel targeted therapies show promise, and further studies are needed to determine the appropriate use of these new agents. Management of endometrial cancer will continue to evolve as clinical trials continue to answer unsolved clinical questions.

  12. Contemporary Clinical Management of Endometrial Cancer

    Science.gov (United States)

    Dinkelspiel, Helen E.; Wright, Jason D.; Lewin, Sharyn N.; Herzog, Thomas J.

    2013-01-01

    Although the contemporary management of endometrial cancer is straightforward in many ways, novel data has emerged over the past decade that has altered the clinical standards of care while generating new controversies that will require further investigation. Fortunately most cases are diagnosed at early stages, but high-risk histologies and poorly differentiated tumors have high metastatic potential with a significantly worse prognosis. Initial management typically requires surgery, but the role and extent of lymphadenectomy are debated especially with well-differentiated tumors. With the changes in surgical staging, prognosis correlates more closely with stage, and the importance of cytology has been questioned and is under evaluation. The roles of radiation in intermediate-risk patients and chemotherapy in high-risk patients are emerging. The therapeutic index of brachytherapy needs to be considered, and the best sequencing of combined modalities needs to balance efficacy and toxicities. Additionally novel targeted therapies show promise, and further studies are needed to determine the appropriate use of these new agents. Management of endometrial cancer will continue to evolve as clinical trials continue to answer unsolved clinical questions. PMID:23864861

  13. Oncogene alterations in endometrial carcinosarcomas.

    Science.gov (United States)

    Biscuola, Michele; Van de Vijver, Koen; Castilla, María Ángeles; Romero-Pérez, Laura; López-García, María Ángeles; Díaz-Martín, Juan; Matias-Guiu, Xavier; Oliva, Esther; Palacios Calvo, José

    2013-05-01

    Endometrial carcinosarcomas are aggressive neoplasias composed of high-grade carcinomatous and sarcomatous elements. The pathogenesis and specific genetic alterations underlying these tumors are still not well known. We analyzed alterations in oncogenes involved in the pathogenesis of endometrial carcinomas that might represent predictive markers for specific therapies. Immunohistochemistry for HER2 (tyrosine kinase-type cell surface receptor HER2) and c-KIT (tyrosine-protein kinase Kit) and fluorescence in situ hybridization for EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma receptor tyrosine kinase) were carried out for 76 endometrial carcinosarcoma samples on sequential tissue microarray sections. Analysis of 238 mutations across 19 common oncogenes was performed on 34 samples using the Sequenom OncoCarta Panel (Sequenom, Hamburg, Germany). We observed EGFR, HER2, and c-KIT expression in 71%, 1.5%, and 2.7% of tumors, respectively. EGFR amplification was detected in 11 of 76 endometrial carcinosarcomas (14.5%). Four samples showed both amplification and aneuploidy (5.2%). ALK amplification together with chromosome 2 polysomy was found in 1.3% of endometrial carcinosarcomas. In total, 23 mutations in 9 different oncogenes were detected in 15 (44.1%) of 34 endometrial carcinosarcomas. Five endometrial carcinosarcomas (14.7%) had 2 or more mutations. Eleven tumors (32.3%) had mutations affecting the PI3K (phosphoinositide-3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog 1) (6 mutations in PIK3CA (PI3K catalytic alpha polypeptide) and 1 in AKT) and/or RAS/BRAF (serine/threonine-protein kinase B-raf) pathway (3 KRAS [kirsten RAS oncogene homolog], 2 NRAS [neuroblastoma RAS viral oncogene homolog], and 1 BRAF). Mutations in PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) and/or KIT were found in 5 endometrial carcinosarcomas (14.7%). Finally, we found mutations in MET (met proto-oncogene [hepatocyte growth factor

  14. Expulsion of Fibroids to the Endometrial Cavity after Magnetic Resonance Imaging-guided High Intensity Focused Ultrasound Surgery (MRgFUS) Treatment of Intramural Uterine Fibroids.

    Science.gov (United States)

    Jeong, Jae-Hyeok; Hong, Gil Pyo; Kim, Yu-Ri; Hong, Da Gyo; Ha, Jae-Eun; Yeom, Jung In; Kim, Eun-Jeong; Kim, Hyung-Il; Lee, Kyu-Sup

    2016-12-01

    This report seeks to introduce some cases of the patients who received magnetic resonance imaging (MRI)-guided high intensity focused ultrasound (HIFU) surgery (MRgFUS)-based intramural uterine fibroids treatment where the post-MRgFUS intramural uterine fibroids decreased in its volume and protruded towards the endometrial cavity to be expelled by hysteroscopy. Of the 157 patients who had received MRgFUS treatment in the Obstetrics and Gynecology of the Hospital from March, 2015 to February, 2016; this study examined 6 of the cases where, after high intensity focused ultrasound treatment, intramural uterine fibroids protruded towards the endometrial cavity to be removed by hysteroscopic myomectomy. The high intensity focused ultrasound utilized in the cases were Philips Achieva 1.5 Tesla MR (Philips Healthcare, Best, The Netherlands) and Sonalleve HIFU system. The volume of fibroids ranged from 26.0 cm3 to 199.5 cm3, averaging 95.6 cm3. The major axis length ranged from 4.0 cm to 8.2 cm, averaging 6.3 cm. Fibroid location in all of the patients was in intramural uterine before treatment but after the high intensity focused ultrasound treatment, the fibroids were observed to protrude towards the endometrial cavity in at least Day 5 or up to Day 73 to allow hysteroscopic myomectomy. In some cases, after an intramural uterine fibroid is treated with MRgFUS, fibroid volume is decreased and the fibroid protrudes towards the endometrial cavity. In this case, hysteroscopic myomectomy can be a useful solution.

  15. Endometrial injury in women undergoing assisted reproductive techniques.

    Science.gov (United States)

    Nastri, Carolina O; Lensen, Sarah F; Gibreel, Ahmed; Raine-Fenning, Nick; Ferriani, Rui A; Bhattacharya, Siladitya; Martins, Wellington P

    2015-03-22

    Implantation of an embryo within the endometrial cavity is a critical step in assisted reproductive techniques (ART). Previous research has suggested that endometrial injury - intentional damage to the endometrium - can increase the probability of pregnancy in women undergoing ART. To assess the effectiveness and safety of endometrial injury performed before embryo transfer in women undergoing ART. We searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American Caribbean Health Sciences Literature (LILACS) and ClinicalTrials.gov. The original search was performed in November 2011, and further searches were done in March 2014 and January 2015. Randomised controlled trials comparing intentional endometrial injury before embryo transfer in women undergoing ART, versus no intervention or a sham procedure. Two independent review authors screened studies and extracted data which were checked by a third review author. Two review authors independently assessed risk of bias. We contacted and corresponded with study investigators as required and analysed data using risk ratio (RR) and a random-effects model. We assessed the quality of the evidence by using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. We included 14 trials that included 1063 women in the intervention groups and 1065 women in the control groups. Thirteen studies compared endometrial injury performed between day 7 of the previous cycle and day 7 of the embryo transfer (ET) cycle versus no injury, and one study compared endometrial injury on the day of oocyte retrieval versus no injury. Overall, eight of the 14 included studies were deemed to be at high risk of bias in at least one domain.In studies comparing endometrial

  16. Triple-tandem high-dose-rate brachytherapy for early-stage medically inoperable endometrial cancer: Initial report on acute toxicity and dosimetric comparison to stereotactic body radiation therapy.

    Science.gov (United States)

    Kauffmann, Greg; Wu, Tianming; Al-Hallaq, Hania; Hasan, Yasmin

    Stereotactic body radiotherapy (SBRT) may be appealing in medically inoperable endometrial cancer to avoid procedural risks. We performed a dosimetric comparison to triple-tandem, high-dose-rate (HDR) brachytherapy. Six consecutive clinical stage I, grade 1-2, medically inoperable endometrial cancer patients were treated with triple-tandem HDR brachytherapy. We report patient factors and acute toxicity. Also, we performed dosimetric comparison to SBRT using both 3D conformal arc (3DArc) and volumetric-modulated arc therapy. D2cc values for normal tissues were calculated and compared to the HDR plans. Median age was 57 years. Patient comorbidities included morbid obesity, congestive heart failure, diabetes, and pulmonary emboli. In three patients who received prior external beam radiation (EBRT), median EBRT and HDR doses were 46 Gy and 20 Gy, respectively. The median dose with HDR brachytherapy monotherapy was 35 Gy. Acute toxicities during EBRT included gastrointestinal (3/3 with grade 1-2) and genitourinary (3/3 with grade 1-2). Acute toxicities during HDR brachytherapy were gastrointestinal (2/6 total with grade 1-2) and genitourinary (2/6 total with grade 1). The mean D2cc/Gy of prescription dose for rectum, sigmoid, and bladder were 0.58, 0.40, and 0.47 respectively. Overall, doses to normal tissues were higher for SBRT plans as compared to HDR. Also, the R50 (ratio of the 50% prescription isodose volume to the PTV) was lowest with HDR brachytherapy. In medically inoperable, clinical stage I endometrial cancer patients with multiple comorbidities, definitive triple-tandem, HDR brachytherapy results in mild acute toxicity. In addition, HDR brachytherapy achieves relatively lower doses to surrounding normal tissues as compared to SBRT. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  17. [Detecting high risk pregnancy].

    Science.gov (United States)

    Doret, Muriel; Gaucherand, Pascal

    2009-12-20

    Antenatal care is aiming to reduce maternal land foetal mortality and morbidity. Maternal and foetal mortality can be due to different causes. Their knowledge allows identifying pregnancy (high risk pregnancy) with factors associated with an increased risk for maternal and/or foetal mortality and serious morbidity. Identification of high risk pregnancies and initiation of appropriate treatment and/or surveillance should improve maternal and/or foetal outcome. New risk factors are continuously described thanks to improvement in antenatal care and development in biology and cytopathology, increasing complexity in identifying high risk pregnancies. Level of risk can change all over the pregnancy. Ideally, it should be evaluated prior to the pregnancy and at each antenatal visit. Clinical examination is able to screen for intra-uterin growth restriction, pre-eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia and abnormal foetal growth; biological exams are used to screen for pre-eclampsia, gestational diabetes, trisomy 21 (for which screening method just changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola, unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most of the preventive strategies have to be initiated during the first trimester or even before conception. Prevention for neural-tube defects, neonatal hypocalcemia and listeriosis should be performed for all women. On the opposite, some measures are concerning only women with risk factors such as prevention for toxoplasmosis, rhesus immunization (which recently changed), tobacco complications and pre-eclampsia and intra-uterine growth factor restriction.

  18. The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia.

    Science.gov (United States)

    Ichinose, Mari; Fujimoto, Akihisa; Osuga, Yutaka; Minaguchi, Takeo; Kawana, Kei; Yano, Tetsu; Kozuma, Shiro

    2013-02-01

    Many patients with endometrial cancer have no children when diagnosed, and thus are reluctant to undergo hysterectomy, hoping to preserve their fertility. Their requirement is met, at least partially, with high-dose medroxyprogesterone acetate that brings good response rate in the treatment of endometrial cancer in the early stage and atypical complex endometrial hyperplasia (EC/ACEH). Actually, a number of successful pregnancies after the conservative treatment have been reported. To conceive, many of them need infertility treatment because of ovulation disorders which might have induced the cancer with unopposed estrogens. However, on the other side, hyperestrogenic status caused by ovulation induction or controlled ovarian stimulation might promote the progression and the recurrence of the disease. This study aimed to assess the effectiveness and safety of infertility treatment after conservative therapy for EC/ACEH, to confirm the significance of fertility-sparing therapy. The patients with EC/ACEH who achieved complete response after high-dose medroxyprogesterone acetate were eligible for this retrospective study. Characteristics of the patients, whether they underwent infertility treatment, conceived, or relapsed, and the interval from complete response to conception or recurrence were retrospectively analyzed. The clinical outcomes of 36 patients were investigated. Twenty-six of them desired to conceive soon after complete response. All of them underwent infertility treatment, and 16 women delivered healthy babies. Kaplan-Meyer curve and log-rank test analysis revealed that women who achieved live birth had a significantly lower risk of recurrence than those without live birth. There was not a significant difference between the patients with and without infertility treatment. Use of ovulation induction drugs after conservative treatment of endometrial cancer did not increase the recurrence of the disease. Moreover, resulting pregnancy seems to have an

  19. Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

    Science.gov (United States)

    Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; Lacroix, Andrea; Tice, Jeffrey A; Chia, Victoria M; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

    2013-02-01

    Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

  20. Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case–control study within the B~FIT cohort

    Science.gov (United States)

    Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea; Tice, Jeffrey A; Chia, Chia; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

    2014-01-01

    Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case–control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n = 15 595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992–1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m2), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (ORT3 vs T1 = 2.96; 95% CI, 1.21–7.25; P trend endometrial cancer. Our findings with leptin suggest that the leptin–BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity–endometrial cancer associations. PMID:23222000

  1. Outcomes of salvage high-dose-rate brachytherapy with or without external beam radiotherapy for isolated vaginal recurrence of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Shuhei Sekii

    2017-05-01

    Full Text Available Purpose: This study was designed to retrospectively analyze outcomes of high-dose-rate (HDR brachytherapy, with or without external beam radiotherapy (EBRT, in patients with vaginal recurrence of endometrial carcinoma, and to identify factors prognostic of patient outcomes. Material and methods : The medical records of all patients who underwent HDR brachytherapy for initial recurrence in the vagina of endometrial cancer after definitive surgery between 1992 and 2014 were retrospectively reviewed. All patients underwent either intracavitary brachytherapy (ICBT or interstitial brachytherapy (ISBT with or without EBRT. Late toxicity was graded using the EORTC (LENT/SOMA scale, revised in 1995. Results : Thirty-seven patients were identified. The median follow-up time was 48 months (range: 6-225 months. Of these 37 patients, 23 underwent ICBT, 14 underwent ISBT, and 26 underwent EBRT. Tumor size at first examination of initial relapse was significantly larger in the ISBT than in the ICBT group. The 4-year respective overall survival (OS, local control (LC, and progression-free survival (PFS rates in the entire cohort were 81.0%, 77.9%, and 56.8%, respectively. The interval between diagnosis of first recurrence and radiotherapy (< 3 months, ≥ 3 months was a significant predictor of LC and PFS. OS and LC rates did not differ significantly in the ICBT and ISBT groups. Two patients experienced grade 2 rectal bleeding, and four experienced grade 2 hematuria. No grade 3 or higher late complications were observed. Conclusions : Salvage HDR brachytherapy is an optimal for treating vaginal recurrence of endometrial carcinoma with acceptable morbidity. Early radiotherapy, including brachytherapy, should be considered for women who experience vaginal recurrence of endometrial cancer.

  2. The prescription pattern of Chinese herbal products that contain dang-qui and risk of endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan: a population-based study.

    Science.gov (United States)

    Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting

    2014-01-01

    The increased practice of traditional Chinese medicine worldwide has raised concerns regarding herb-drug interactions. We analyzed the usage of Chinese herbal products containing dang-qui and investigated whether dang-qui therapy increases endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. All patients newly diagnosed with invasive breast cancer who received tamoxifen treatment from January 1, 1998, to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service and type of Chinese herbal products containing dang-qui prescribed across the 31,970 survivors were evaluated. Logistic regression method was employed to estimate the odds ratios for utilization of Chinese herbal products containing dang-qui. Cox proportional hazard regression was performed to calculate the hazard ratio of endometrial cancer associated with dang-qui use within the cohort. Almost one in two study subjects had used dang-qui. Among 31,938 tamoxifen-treated breast cancer survivors, 157 cases of subsequent endometrial cancer were identified. The hazard ratio for development of endometrial cancer among breast cancer survivors aged 20-79 years who had taken dang-qui after tamoxifen treatment was decreased compared to survivors who had never used dang-qui (HR: 0.61, 95%CI: 0.44-0.84). To minimise potential confounding factors, women with breast cancer in the reproductive age were excluded from further analysis, and the negative relationship between dang-qui consumption and subsequent endometrial cancer among breast cancer survivors aged 55-79 years was still observed, although not significantly (HR: 0.74, 95%CI: 0.46-1.17). Dang-qui consumption is common among breast cancer survivors aged 20-79 years and seems decrease the risk of subsequent endometrial cancer after less than a cumulative dose of 7,500 mg of tamoxifen treatment.

  3. Endometrial haemostasis and menstruation.

    Science.gov (United States)

    Davies, Joanna; Kadir, Rezan A

    2012-12-01

    Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

  4. Body mass index, physical activity, and television time in relation to mortality risk among endometrial cancer survivors in the NIH-AARP Diet and Health Study cohort.

    Science.gov (United States)

    Arem, Hannah; Pfeiffer, Ruth M; Moore, Steven C; Brinton, Louise A; Matthews, Charles E

    2016-11-01

    Endometrial cancer (EC) survivors are the second largest group of female cancer survivors in the USA, with high prevalence of obesity and physical inactivity. While higher pre-diagnosis body mass index (BMI) has been associated with higher all-cause and disease-specific mortality, pre-diagnosis physical activity has shown mixed evidence of an association with mortality. However, the association between BMI, physical activity, and TV viewing measured after diagnosis and mortality risk among EC survivors is unknown. We identified 580 women with EC in the NIH-AARP Diet and Health Study who completed a post-diagnosis questionnaire on BMI, leisure time moderate- to vigorous-intensity physical activity (MVPA), and TV viewing. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. With a median follow-up time of 7.1 years, we observed 91 total deaths. We found a positive association between BMI ([Formula: see text] = 2.14, 95% CI 1.08-4.24 and mortality, and no statistically significant association between TV viewing (HR5+ vs. <3 h/day = 1.46, 95% CI 0.86-2.46) and mortality nor MVPA with mortality (HR15+ vs. 0 MET h/week = 0.72, 95% CI 0.43-1.21) after adjusting for tumor characteristics and demographic factors. Further adjustment for lifestyle and health status attenuated BMI associations ([Formula: see text] = 1.47, 95% CI 0.71-3.07), but strengthened the association between TV viewing and mortality (HR5+ vs. <3 h/day = 2.28, 95% CI 1.05-4.95). Our results suggest that higher post-diagnosis BMI and TV viewing may be associated with higher mortality risk among EC patients, but that there may be complicated interrelationships between lifestyle factors of BMI, PA, and TV viewing and the mediating role of health status that need to be clarified.

  5. Exercise Training Prevents Endometrial Hyperplasia and Biomarkers for Endometrial Cancer in Rat Model of Type 1 Diabetes

    OpenAIRE

    Al-Jarrah, Muhammed; Matalka, Ismail; Aseri, Hasan Al; Mohtaseb, Alia; Smirnova, Irina V; Novikova, Lesya; Stehno-Bittel, Lisa; AlKhateeb, Ahed

    2010-01-01

    Background Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen r...

  6. Fertility preservation in young women with endometrial carcinoma; report of three cases

    Directory of Open Access Journals (Sweden)

    Mousavi A.S

    2007-06-01

    Full Text Available Background: Although endometrial cancer is primarily a disease of the postmenopausal female, 25% of patients are premenopausal, with 3-5% in women 40 years old or younger. The younger group of women with endometrial carcinoma are frequently nulligravid with a history of infertility, and a strong desire to preserve fertility. This may pose a therapeutic dilemma for both patients and treating physician. Case report: We reported 3 young patients with atypical; complex hyperplasia or early stage endometrial cancer that treated with conservative hormonal therapy. Conclusion: Medical treatment of young patients with endometrial carcinoma and complex atypical hyperplasia who wish to preserve fertility is a reasonable and appealing option. A comprehensive evaluation prior to counseling the patient should include A complete history and physical examination. A formal D&C with review of history with an experienced gyn-onc pathologist. Evaluation of the pelvic and abdomen preferably with contrast-enhanced MRI or transvaginal ultrasound. In patients found to have a clinical stage I grade I tumor and who want to preserve fertility , thorough counseling include risks and benefits, and explanation that the data is partial and incomplete due to the lack of appropriate controlled studies is mandatory. In patients considered for medical treatment, a high dose progestin regimen should be started with endometrial sampling every 3 months until complete regression of the tumor is documented. Although most responses are long standing, there is a small risk of progression during or after cessation of progestin therapy.

  7. The Emerging Genomic Landscape of Endometrial Cancer

    Science.gov (United States)

    Le Gallo, Matthieu; Bell, Daphne W.

    2014-01-01

    BACKGROUND Endometrial cancer is responsible for ~74,000 deaths amongst women worldwide each year. It is a heterogeneous disease that consists of multiple different histological subtypes. In the United States, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors. CONTENT Herein we review the current state of knowledge of the somatic genomic alterations that are present in serous and endometrioid endometrial tumors. We present this knowledge in a historical context – reviewing the genomic alterations that have been identified over the past two decades or more, from studies of individual genes and proteins, followed by a review of very recent studies that have conducted comprehensive, systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas. SUMMARY The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has resulted in the first comprehensive molecular classification of these tumors and has distinguished four molecular subgroups: a POLE ultramutated subgroup, a hypermutated/microsatellite unstable subgroup, a copy number low/microsatellite stable subgroup, and a copy number high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors. PMID:24170611

  8. Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer

    NARCIS (Netherlands)

    Alonso-Alconada, Lorena; Muinelo-Romay, Laura; Madissoo, Kadri; Diaz-Lopez, Antonio; Krakstad, Camilla; Trovik, Jone; Wik, Elisabeth; Hapangama, Dharani; Coenegrachts, Lieve; Cano, Amparo; Gil-Moreno, Antonio; Chiva, Luis; Cueva, Juan; Vieito, Maria; Ortega, Eugenia; Mariscal, Javier; Colas, Eva; Castellvi, Josep; Cusido, Maite; Dolcet, Xavier; Nijman, Hans W.; Bosse, Tjalling; Green, John A.; Romano, Andrea; Reventos, Jaume; Lopez-Lopez, Rafael; Salvesen, Helga B.; Amant, Frederic; Matias-Guiu, Xavier; Moreno-Bueno, Gema; Abal, Miguel

    2014-01-01

    Background: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in

  9. Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer

    Science.gov (United States)

    2017-09-08

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm; Recurrent Uterine Corpus Carcinoma

  10. Urolithin A suppresses the proliferation of endometrial cancer cells by mediating estrogen receptor-α-dependent gene expression.

    Science.gov (United States)

    Zhang, Wei; Chen, Jo-Hsin; Aguilera-Barrantes, Irene; Shiau, Chung-Wai; Sheng, Xiugui; Wang, Li-Shu; Stoner, Gary D; Huang, Yi-Wen

    2016-11-01

    Obese and overweight women are at high risk of developing endometrial cancer; indeed, many of endometrial cancer patients are obese. The increased number and size of adipocytes due to obesity elevate levels of circulating estrogens that stimulate cell proliferation in the endometrium. However, black raspberries are a promising approach to preventing endometrial cancer. We examined 17 black raspberry constituents and metabolites (10 μM or 10 μg/mL, 48 h) for their ability to prevent endometrial cancer cells from proliferating. Urolithin A (UA) was most able to suppress proliferation in a time- and dose-dependent manner (p endometrial cancer cells. UA enhanced the expression of ERβ, PGR, pS2, GREB1 while inhibiting the expression of ERα and GRIP1. Coincubating UA-treated cells with the estrogen antagonist ICI182,780 abolished UA's estrogenic effects. Knocking down ERα suppressed PGR, pS2, and GREB gene expression but increased GRIP1 expression. Thus, UA's actions appear to be mediated through ERα. This study suggests that UA modulates ERα-dependent gene expression, thereby inhibiting endometrial cancer proliferation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Endometrial ablation: first- vs. second-generation techniques.

    Science.gov (United States)

    Angioni, Stefano; Pontis, Alessandro; Nappi, Luigi; Sedda, Federica; Sorrentino, Felice; Litta, Pietro; Haimovich, Sergio; Melis, Gian B

    2016-04-01

    Endometrial ablation is a procedure that surgically destroys (ablates) the lining of the uterus (endometrium). The goal of endometrial ablation is to reduce menstrual flow. In some women, menstrual flow may stop completely. In some cases, endometrial ablation may be an alternative to hysterectomy. There are several techniques used to perform endometrial ablation, including electrical or electrocautery ablation, in which an electric current travels through a wire loop or rollerball is applied to the endometrial lining to cauterize the tissue; hydrothermal ablation, in which heated fluid is pumped into the uterus and destroys the endometrial lining via high temperatures; balloon therapy ablation, in which a balloon at the end of a catheter is inserted into the uterus and filled with fluid, which is then heated to the point that the endometrial tissues are eroded away; radiofrequency ablation in which a triangular mesh electrode is expanded to fill the uterine cavity, at which point the electrode delivers an electrical current and destroys the endometrial lining; cryoablation (freezing), in which a probe uses extremely low temperatures to freeze and destroy the endometrial tissues; and microwave ablation, in which microwave energy is delivered through a slender probe inserted into the uterus and destroys the endometrial lining. The purpose of this systematic review was to evaluate the feasibility, safety, and efficacy of endometrial ablation performed with first- and second-generation techniques. A literature search in PubMed from January 2000 to September 2015 was performed using the keywords endometrial ablation, menorrhagia, and heavy menstrual bleeding. Results were restricted to systematic reviews, randomized control trials (RCT)/controlled clinical trials, and observational studies written in English from January 2000 to September 2015. There is no evidence that either broad category is more effective than the other in reducing HMB, and there is no evidence that

  12. Lower preoperative quality of life increases postoperative risk of adverse events in women with endometrial cancer: results from the LACE trial.

    Science.gov (United States)

    Baker, Jannah; Janda, Monika; Gebski, Val; Forder, Peta; Hogg, Russell; Manolitsas, Tom; Obermair, Andreas

    2015-04-01

    To examine the association between preoperative quality of life (QoL) and postoperative adverse events in women treated for endometrial cancer. 760 women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery. This analysis includes women with preoperative QoL measurements, from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, and who were followed up for at least 6 weeks after surgery (n=684). The outcomes for this study were defined as (1) the occurrence of moderate to severe adverse events within 6 months (Common Toxicology Criteria (CTC) grade≥3); and (2) any serious adverse event (SAE). The association between preoperative QoL and the occurrence of AE was examined, after controlling for baseline comorbidity and other factors. After adjusting for other factors, odds of occurrence of AE of CTC grade≥3 were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.00-1.03, p=0.030), which was driven by physical well-being (PWB) (OR=1.09, 95% CI 1.04-1.13, p=0.0002) and functional well-being subscales (FWB) (OR=1.04, 95% CI 1.00-1.07, p=0.035). Similarly, odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.01-1.04, p=0.011), baseline PWB (OR=1.11, 95% CI 1.06-1.16, p<0.0001) or baseline FWB subscales (OR=1.05, 95% CI 1.01-1.10, p=0.0077). Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery. Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council, Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare

  13. Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients.

    Science.gov (United States)

    Méndez-López, Luis Fernando; Dávila-Rodríguez, Martha Imelda; Zavala-Pompa, Angel; Torres-López, Ernesto; González-Martínez, Blanca Edelia; López-Cabanillas-Lomelí, Manuel

    2013-07-01

    The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer.

  14. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Damast, Shari, E-mail: shari.damast@yale.edu [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goldfarb, Shari [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Eaton, Anne; Patil, Sujata [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mosenkis, Jeffrey [Department of Comparative Human Development, University of Chicago, Chicago, Illinois (United States); Bennett, Antonia [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Atkinson, Thomas [Department of Psychiatry, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jewell, Elizabeth; Leitao, Mario; Barakat, Richard; Carter, Jeanne [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Basch, Ethan [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2012-10-01

    Purpose: We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. Methods and Materials: A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from <6 months to >5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. Results: SD was reported by 81% of respondents. The mean ({+-} standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 ({+-}2.0); orgasm, 2.5 ({+-}2.4); desire, 2.4 ({+-}1.3); arousal, 2.2 ({+-}2.0); dryness, 2.1 ({+-}2.1); and pain, 1.9 ({+-}2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, -7.1 points; 95% CI, -11.2 to -3.1; P<.001), lack of vaginal lubricant use (effect size, -4.4 points; 95% CI, -8.7 to -0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, -4.6 points; 95% CI, -9.3-0.2; P=.059). Conclusions: The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

  15. Advanced and Recurrent Endometrial Cancer; current concepts of treatment

    NARCIS (Netherlands)

    F.H. van Wijk (Heidy)

    2008-01-01

    textabstractEndometrial cancer is the most common gynecological malignancy in Western Countries. In the United States approximately 39,000 cases will be diagnosed in 2007 and 7,400 deaths will occur. Women have a 2.6% lifetime risk of developing endometrial cancer and it accounts for 6% of all

  16. GPR54 is a target for suppression of metastasis in endometrial cancer.

    Science.gov (United States)

    Kang, Hyun Sook; Baba, Tsukasa; Mandai, Masaki; Matsumura, Noriomi; Hamanishi, Junzo; Kharma, Budiman; Kondoh, Eiji; Yoshioka, Yumiko; Oishi, Shinya; Fujii, Nobutaka; Murphy, Susan K; Konishi, Ikuo

    2011-04-01

    Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, kisspeptin (KISS1), and its endogenous receptor, GPR54, has been reported in several cancers, but the significance of the KISS1/GPR54 axis in endometrial cancer metastasis has not been clarified. Metastin-10 is the minimal bioactive sequence of genetic products of KISS1. Clinicopathological analysis of 92 endometrial cancers revealed overall survival is improved in cancers with high expression of GPR54 (P GPR54 expression is associated with known prognostic factors including FIGO stage, grade, and deep myometrial invasion. Through RNAi and microarray analyses, metastin-10 was predicted to suppress metastasis of GPR54-expressing endometrial cancers in vivo. Methylation analysis revealed GPR54 is epigenetically regulated. Metastin-GPR54 axis function was restored following treatment with the DNA hypomethylating agent 5-aza-DC. These data suggest that metastin-10 may be effective at inhibiting the metastatic spread of endometrial cancers in combination with demethylating agents to induce GPR54 expression.

  17. Controversies in the Management of Endometrial Carcinoma: An Update

    Directory of Open Access Journals (Sweden)

    Mohamed K. Mehasseb

    2012-01-01

    Full Text Available Endometrial carcinoma is the commonest type of female genital tract malignancy in the developed countries. Endometrial carcinoma is usually confined to the uterus at the time of diagnosis and as such usually carries an excellent prognosis with high curability. Our understanding and management of endometrial cancer have continuously developed. Current controversies focus on screening and early detection, the extent of nodal surgery, and the changing roles of radiation therapy and chemotherapy and will be discussed in this paper.

  18. [High dynamic risk cystoceles].

    Science.gov (United States)

    Salinas Casado, Jesús; Méndez Rubio, Santiago; Virseda Chamorro, Miguel; Pelaquim, Humberto; Silmi Moyano, Angel

    2010-06-01

    To assess the bladder compliance in a series of cystoceles referred for urodynamic study. Retrospective study of a series of patients with cystocele undergoing medical history, videurodynamic study, pelvic MRI and lower urinary tract, urological ultrasound and cystoscopy. We Excluded cases with neurogenic dysfunction and urinary infection. The terminology followed the criteria of the ICS, if not specified otherwise. The series includes 3333 cases of cystocele 616 of which are grade III cystocele. There were 3 cases with low bladder compliance; this is 0.0009% of total (1:1000) and 0.5% of grade III cystocele (1:200) All cases of cystocele whith low compliance were associated with feeling of a bulk in the vagina and functional symptoms of lower urinary tract(LUTS). No urinary incontinence was related to cough. These patients also showed urodynamic alterations in the voiding phase, type hypo / acontractile detrusor and postvoid residual. The patients were subjected to various techniques of abdominal and transvaginal cystocele repair (with preventive anti-incontinence surgery), getting a vagina bulk disappearance, improvement of symptoms of lower urinary tract function, normalization of bladder compliance and detrusor contractility, with elimination of the postvoid residual. Although they are not frequent, high-risk cystoceles should be discarded in high-grade cystocele that apart from low bladder accommodation, have a hipo/acontractile detrusor and postvoid residual. Surgical correction of cystocele not only reduces the bulk and LUTS, but normalizes urodynamic alterations.

  19. PGK1 and GRP78 overexpression correlates with clinical significance and poor prognosis in Chinese endometrial cancer patients.

    Science.gov (United States)

    Guo, Suiqun; Xiao, Yanyi; Li, Danqing; Jiang, Qingping; Zhu, Litong; Lin, Dan; Jiang, Huiping; Chen, Wei; Wang, Lijing; Liu, Chunhua; Fang, Weiyi; Lin, Li

    2018-01-02

    The aim of this study was to measure the expression patterns of PGK1 and GRP78 in normal endometrial tissues and endometrial carcinoma, and associations between their combined effects and the pathological features of endometrial carcinoma. We used 30 normal endometrial tissue samples and 130 endometrial carcinoma samples, and separately evaluated PGK1 and GRP78 protein expression by immunohistochemistry. Scores ranging from 0 to 9 were obtained by multiplying the percentage of positive cells by the staining intensity (0-3). Immunohistochemical analysis revealed increased PGK1 and GRP78 expression in the cytoplasm of endometrial carcinoma cells compared with that in normal endometrial tissues. High PGK1 expression positively correlated with the FIGO stage ( P endometrial carcinoma patients ( P endometrial carcinoma patients correlated significantly with the lymph node status ( P endometrial carcinoma progression.

  20. Current strategies in the diagnosis of endometrial cancer.

    Science.gov (United States)

    Tzur, Tamar; Kessous, Roi; Weintraub, Adi Y

    2017-07-01

    Endometrial cancer is the most common gynecological malignancy in developed countries. There are no uniform recommendations for endometrial cancer screening in the general population. Therefore, it is of paramount importance that the primary physician profoundly understands, and is familiar with the methods for prevention and early detection of endometrial cancer. The aim of this review is to provide the primary physician with a toolbox to reach these goals. We performed a systemic review to summarize the current strategies to diagnose and prevent endometrial cancer. Many published articles from the last years were identified and included. A systematic review that summarizes the important subjects in the diagnosis and prevention of endometrial cancer. Maintaining a high index of suspicion and obtaining endometrial biopsies from all suspected patients is the key for achieving a timely diagnosis.

  1. Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study

    Science.gov (United States)

    Bartels, Peter H; Garcia, Francisco AR; Trimble, Cornelia L; Kauderer, James; Curtin, John; Lim, Peter C; Hess, Lisa M; Silverberg, Steven; Zaino, Richard J; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S

    2014-01-01

    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 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 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 lesions might serve as criterion for assessment of risk for the development of invasive disease. PMID:22155796

  2. Xenografted tissue models for the study of human endometrial biology.

    Science.gov (United States)

    Kuokkanen, Satu; Zhu, Liyin; Pollard, Jeffrey W

    The human endometrium undergoes extensive morphological, biochemical and molecular changes under the influence of female sex steroid hormones. Besides the fact that estrogen stimulates endometrial cell proliferation and progesterone inhibits this proliferation and induces differentiation, there is limited knowledge about precise molecular mechanisms underlying human endometrial biology. The importance of paracrine signaling in endometrial physiology explains why in vitro culture of endometrial cells has been challenging. Researchers, therefore, have developed alternative experimental in vivo models for the study of endometrial biology. The objective of this review is to summarize the recent developments and work on these in vivo endometrial research models. The in vivo recombinant tissue models in which wild-type endometrial cells are combined with endometrial cells from a gene-targeted mouse strain followed by xenografting to host mice have been critical in confirming the significance of paracrine signaling between the epithelium and stroma in the growth regulation of the endometrium. Additionally, these studies have uncovered differences between the mouse and human, emphasizing the need for the development of experimental models specifically of the human endometrium. Recently, xenotransplants of human endometrial fragments into the subcutaneous space of host mice and endometrial xenografts of dissociated and recombined epithelial and stromal cells beneath the kidney capsule of immunodeficient host mice have proven to be highly promising tools for in vivo research of endometrial functions. For the first time, the latter approach provides an immense opportunity for the application of genome engineering, such as targeted ablation of endometrial genes for example by using CRISPR/CAS9 system. This research will begin to elucidate the functional role of specific genes in this complex tissue. Another advantage of xenotransplantation and xenograft models of the human

  3. Life-style and metformin for the prevention of endometrial pathology in postmenopausal women.

    Science.gov (United States)

    Campagnoli, Carlo; Abbà, Chiara; Ambroggio, Simona; Brucato, Tiziana; Pasanisi, Patrizia

    2013-02-01

    In western women, the endometrium is frequently exposed, even after menopause, to the endogenous hormonal stimulation. Such a stimulation increases the risk of pathologic conditions such as endometrial hyperplasia and type I (endometrioid) endometrial adenocarcinoma. Metabolic syndrome, obesity, insulin resistance and type II diabetes promote the endometrial stimulation, and are recognized risk factors for endometrial cancer. Furthermore, chronic hyperinsulinemia linked both to obesity and metabolic syndrome influences endometrial proliferation through direct and indirect actions. Intentional weight loss, calorie restriction and physical activity are associated with a reduced risk of the endometrial pathology. Biological mechanisms include reduction in insulin and sex steroid hormone levels. In addition to life-style modifications, the antidiabetic metformin may be proposed as preventive agent. Metformin reduces the metabolic syndrome, lowers insulin and testosterone levels in postmenopausal women, and it is a potent inhibitor of endometrial cancer cell proliferation.

  4. Perceptions of high risk sports.

    Science.gov (United States)

    Pedersen, D M

    1997-10-01

    High risk sports were rated as to risk, appeal, and likelihood of participation by 282 men and 162 women. Ascending order of perceived risk was skiing, scuba diving, bungee jumping, rock climbing, motorcycle racing, hang gliding, cliff jumping, and skydiving. Profile analysis showed stated likelihood of participation to be directly related to appeal and inversely related to perceived risk.

  5. Stem cell-like properties of the endometrial side population: implication in endometrial regeneration.

    Directory of Open Access Journals (Sweden)

    Hirotaka Masuda

    Full Text Available BACKGROUND: The human endometrium undergoes cyclical regeneration throughout a woman's reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerative capacity of the human endometrium at eutopic and ectopic sites suggests the existence of stem/progenitor cells and a unique angiogenic system. The objective of this study was to isolate and characterize putative endometrial stem/progenitor cells and to address how they might be involved in the physiology of endometrium. METHODOLOGY/PRINCIPAL FINDINGS: We found that approximately 2% of the total cells obtained from human endometrium displayed a side population (SP phenotype, as determined by flow cytometric analysis of Hoechst-stained cells. The endometrial SP (ESP cells exhibited preferential expression of several endothelial cell markers compared to endometrial main population (EMP cells. A medium specific for endothelial cell culture enabled ESP cells to proliferate and differentiate into various types of endometrial cells, including glandular epithelial, stromal and endothelial cells in vitro, whereas in the same medium, EMP cells differentiated only into stromal cells. Furthermore, ESP cells, but not EMP cells, reconstituted organized endometrial tissue with well-delineated glandular structures when transplanted under the kidney capsule of severely immunodeficient mice. Notably, ESP cells generated endothelial cells that migrated into the mouse kidney parenchyma and formed mature blood vessels. This potential for in vivo angiogenesis and endometrial cell regeneration was more prominent in the ESP fraction than in the EMP fraction, as the latter mainly gave rise to stromal cells in vivo. CONCLUSIONS/SIGNIFICANCE: These results indicate that putative endometrial stem cells are highly enriched in the ESP cells. These unique characteristics suggest that

  6. Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management.

    Science.gov (United States)

    Nwanodi, Oroma

    2017-07-08

    Globally, endometrial cancer is the sixth leading cause of female cancer-related deaths. Non-atypical endometrial hyperplasia (EH), has a lifetime progression rate to endometrial cancer ranging from less than 5%, if simple without atypia, to 40%, if complex with atypia. Site specific, long-acting intrauterine devices (IUDs) provide fertility sparing, progestin-based EH medical management. It is unclear which IUD is most beneficial, or if progesterone sensitizing metformin offers improved outcomes. For resolution, PubMed searches for "Mirena" or "Metformin," "treatment," "endometrial hyperplasia," or "stage 1 endometrial cancer," were performed, yielding 33 articles. Of these, 19 articles were included. The 60 mg high-dose frameless IUD/20 mcg levonorgestrel has achieved sustained regression of Grade 3 endometrial intraepithelial neoplasia for 14 years. Case series on early stage endometrial cancer (EC) treatment with IUDs have 75% or greater regression rates. For simple through complex EH with atypia, the 52 mg-IUD/10-20 mcg-LNG-14t has achieved 100% complete regression in 6-months. Clearly, IUDs have an outcome advantage over oral progestins. However, studies on metformin for EH, and of progestins or metformin for early stage EC management are underpowered, with inadequate dose ranges to achieve significant differences in, or optimal outcomes for, the treatment modalities. Therefore, outcomes from the feMMe trial for the 52 mg-IUD/10-20 mcg-LNG-14t and metformin will fill a gap in the literature.

  7. Endometrial cancer after endometrial ablation versus medical management of abnormal uterine bleeding

    Science.gov (United States)

    Dood, Robert L.; Gracia, Clarisa R.; Sammel, Mary D.; Haynes, Kevin; Senapati, Suneeta; Strom, Brian L.

    2014-01-01

    Study Objective To investigate whether endometrial ablation carries an increased risk or delayed diagnosis of endometrial cancer compared to medical management for abnormal uterine bleeding. Design A multi-centered retrospective cohort study comparing rates of endometrial cancer in women who underwent treatment for abnormal uterine bleeding. Design Classification Canadian Task-Force Classification II-2 Setting This study was conducted using data from The Health Improvement Network (THIN), a representative population-based cohort of patients in 495 outpatient General Practitioner practices in the UK. Participants Women >25 years of age with an abnormal uterine bleeding diagnosis between June 1994 and September 2010. Interventions Endometrial ablation, medical management, or both. Measurements and Main Results A total of 234,721 women met study inclusion and exclusion criteria, 4,776 of whom underwent endometrial ablation and the remaining 229,945 underwent medical management. Cox models compared endometrial cancer rates between ablation and medical management groups using hazard ratios (HRs). To investigate a possible diagnostic delay, the median time from bleeding diagnosis to endometrial cancer diagnosis among women who developed endometrial cancer was compared using the Mann-Whitney U test. All statistical tests were two-tailed with α=.05. Over a median observation time of 4.07 years (IQR, 1.88-7.17), three and 601 women developed endometrial cancer in the ablation and medical management groups, respectively (ablation HR, 0.45; 95% CI, 0.15-1.40; p=.17). Median time to diagnosis was 237 and 299 days (ablation IQR, 155-1350; medical management IQR, 144-1,133.5; p=.99) in the ablation and medical management groups, respectively. Adjusted and sensitivity analyses did not change the results. Conclusions No difference was seen in endometrial cancer rates, nor was there a delay in diagnosis when comparing endometrial ablation versus medical management. Further studies

  8. Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma.

    Science.gov (United States)

    Deng, Lu; Gao, Yiping; Li, Xiao; Cai, Mingbo; Wang, Huimin; Zhuang, Huiyu; Tan, Mingzi; Liu, Shuice; Hao, Yingying; Lin, Bei

    2015-09-11

    It is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What's more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma. The expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining. ANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p endometrial carcinoma (p endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.

  9. Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data

    NARCIS (Netherlands)

    Nout, Remi A.; Putter, Hein; Jurgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Lutgens, Ludy C. H. W.; van der Steen-Banasik, Elzbieta M.; Mens, Jan Willem M.; Slot, Annerie; Kroese, Marika C. Stenfert; Nijman, Hans W.; van de Poll-Franse, Lonneke V.; Creutzberg, Carien L.

    Background: The PORTEC-2 trial showed efficacy and reduced side-effects of vaginal brachy-therapy (VBT) compared with external beam pelvic radiotherapy (EBRT) for patients with high-intermediate risk endometrial cancer. The current analysis was done to evaluate long-term health related quality of

  10. High-Risk Pregnancy

    Science.gov (United States)

    ... risk? » Related A-Z Topics Diabetes Pregnancy Loss Preeclampsia and Eclampsia NICHD News Spotlights Podcast: NICHD launches PregSource to learn more about pregnancy News Release: NIH Begins Large HIV Treatment Study in Pregnant Women Spotlight: Zika Research after ...

  11. Comparison of 2D and 3D Imaging and Treatment Planning for Postoperative Vaginal Apex High-Dose Rate Brachytherapy for Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Russo, James K. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Armeson, Kent E. [Division of Biostatistics and Epidemiology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Richardson, Susan, E-mail: srichardson@radonc.wustl.edu [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2012-05-01

    Purpose: To evaluate bladder and rectal doses using two-dimensional (2D) and 3D treatment planning for vaginal cuff high-dose rate (HDR) in endometrial cancer. Methods and Materials: Ninety-one consecutive patients treated between 2000 and 2007 were evaluated. Seventy-one and 20 patients underwent 2D and 3D planning, respectively. Each patient received six fractions prescribed at 0.5 cm to the superior 3 cm of the vagina. International Commission on Radiation Units and Measurements (ICRU) doses were calculated for 2D patients. Maximum and 2-cc doses were calculated for 3D patients. Organ doses were normalized to prescription dose. Results: Bladder maximum doses were 178% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were no different than ICRU doses (p = 0.22). Two-cubic centimeter doses were 59% of maximum doses (p < 0.0001). Rectal maximum doses were 137% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 87% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 64% of maximum doses (p < 0.0001). Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final bladder dose to within 10% for 44%, 59%, 83%, 82%, and 89% of patients by using the ICRU dose, and for 45%, 55%, 80%, 85%, and 85% of patients by using the maximum dose, and for 37%, 68%, 79%, 79%, and 84% of patients by using the 2-cc dose. Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final rectal dose to within 10% for 100%, 100%, 100%, 100%, and 100% of patients by using the ICRU dose, and for 60%, 65%, 70%, 75%, and 75% of patients by using the maximum dose, and for 68%, 95%, 84%, 84%, and 84% of patients by using the 2-cc dose. Conclusions: Doses to organs at risk vary depending on the calculation method. In some cases, final dose accuracy appears to plateau after the third fraction, indicating that simulation and planning may not be necessary in all fractions. A clinically relevant level of accuracy should be determined and further research conducted to address

  12. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship.

    Science.gov (United States)

    Fader, Amanda Nickles; Arriba, Lucybeth Nieves; Frasure, Heidi E; von Gruenigen, Vivian E

    2009-07-01

    Endometrial cancer is the most common gynecologic malignancy in the Western world and is strongly associated with obesity. Despite the fact that most cases are diagnosed in early, more favorable stages, endometrial cancer incidence and mortality rates are on the rise. Morbidly obese women with endometrial cancer are more likely to die of their co-morbidities and also of their cancers when compared to their leaner cohorts. Given the increasing rates of morbid obesity in the United States, it is essential to develop appropriate screening tools and guidelines to reduce cancer morbidity and death amongst this group. Through an analysis of the existing literature, we present a review of the epidemiologic trends in obesity and endometrial cancer, discuss the promising role of screening biomarker studies, review prevention efforts and modifiable risk factors, and ways in which health outcomes and quality of life for endometrial cancer survivors may be optimized.

  13. Obesity and age at diagnosis of endometrial cancer.

    Science.gov (United States)

    Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Levitt, Joshua; Girda, Eugenia; Goldfinger, Mendel; Goldberg, Gary L; Einstein, Mark H

    2014-08-01

    Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, Page of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. II.

  14. Window of implantation transcriptomic stratification reveals different endometrial subsignatures associated with live birth and biochemical pregnancy.

    Science.gov (United States)

    Díaz-Gimeno, Patricia; Ruiz-Alonso, Maria; Sebastian-Leon, Patricia; Pellicer, Antonio; Valbuena, Diana; Simón, Carlos

    2017-10-01

    To refine the endometrial window of implantation (WOI) transcriptomic signature by defining new subsignatures associated to live birth and biochemical pregnancy. Retrospective cohort study. University-affiliated in vitro fertilization clinic and reproductive genetics laboratory. Healthy fertile oocyte donors (n = 79) and patients with infertility diagnosed by Endometrial Receptivity Analysis (n = 771). None. WOI transcriptomic signatures associated with specific reproductive outcomes. The retrospective cohort study was designed to perform a prediction model based on transcriptomic clusters for endometrial classification (training set, n = 529). The clinical follow-up set in the expected WOI (n = 321) was tested with the transcriptomic predictor to detect WOI variability and the pregnancy outcomes associated with these subsignatures (n = 228). The endometrial receptivity signature was redefined into four WOI transcriptomic profiles. This stratification identified an optimal endometrial receptivity (RR) signature resulting in an ongoing pregnancy rate (OPR) of 80% in terms of live birth, as well as a late receptive-stage (LR) signature with a potential high risk of 50% biochemical pregnancy. Abnormal down-regulation of the cell cycle was the main dysregulated function among the 22 genes associated with biochemical pregnancy. The major differences between the WOI transcriptomic stratification were in the OPR and biochemical pregnancy rate. The OPR ranged from 76.9% and 80% in the late prereceptive (LPR) and RR signatures, respectively, versus 33.3% in the LR. The biochemical pregnancy rate was 7.7% and 6.6% in LPR and RR, respectively, but 50% in LR, which highlights the relevance of endometrial status in the progression of embryonic implantation. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Genetic risk score Mendelian randomization shows obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer

    Science.gov (United States)

    Painter, Jodie N; O’Mara, Tracy A; Marquart, Louise; Webb, Penelope M; Attia, John; Medland, Sarah E; Cheng, Timothy; Dennis, Joe; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley V; Beckmann, Matthias W; Ekici, Arif B; Fasching, Peter A; Hein, Alexander; Rübner, Matthias; Czene, Kamila; Darabi, Hatef; Hall, Per; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Lambrechts, Diether; Neven, Patrick; Cunningham, Julie M; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica MJ; Ashton, Katie A; Otton, Geoffrey; Proietto, Anthony; Mints, Miriam; Tham, Emma; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2016-01-01

    Background The strongest known risk factor for endometrial cancer (EC) is obesity. To determine whether single nucleotide polymorphisms (SNPs) associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with EC risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and EC in 6,609 cases and 37,926 country-matched controls. Methods Logistic regression analysis and fixed-effects meta-analysis were used to test for associations between EC risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for EC was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. Results The BMIwGRS was significantly associated with EC risk (P=3.4×10−17). Scaling the effect of the BMIwGRS on EC risk by its effect on BMI, the EC odds ratio (OR) per 5kg/m2 of genetically predicted BMI was 2.06 (95% confidence interval(CI)=1.89–2.21), larger than the observed effect of BMI on EC risk (OR=1.55, 95%CI 1.44–1.68, per 5kg/m2). The association attenuated but remained significant after adjusting for BMI (OR=1.22, 95%CI=1.10–1.39,P=5.3×10−4). There was evidence of directional pleiotropy (P=1.5×10−4). BMI SNP rs2075650 was associated with EC at study-wide significance (P<4.0×10−4), independent of BMI. EC was not significantly associated with individual WHR SNPs or the WHRwGRS. Conclusions BMI, but not WHR, is causally associated with EC risk, with evidence that some BMI-associated SNPs alter EC risk via mechanisms other than measurable BMI. Impact The causal association between BMI SNPs and EC has possible implications for EC risk modeling. PMID:27550749

  16. Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case-control study in nonsmoking postmenopausal women from the EPIC cohort.

    Science.gov (United States)

    Obón-Santacana, Mireia; Freisling, Heinz; Peeters, Petra H; Lujan-Barroso, Leila; Ferrari, Pietro; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Baglietto, Laura; Turzanski-Fortner, Renee; Katzke, Verena A; Boeing, Heiner; Quirós, J Ramón; Molina-Portillo, Elena; Larrañaga, Nerea; Chirlaque, María-Dolores; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Merritt, Melissa A; Gunter, Marc J; Trichopoulou, Antonia; Lagiou, Pagona; Naska, Androniki; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Fiano, Valentina; Galassom, Rocco; Bueno-de-Mesquita, H B As; Onland-Moret, N Charlotte; Idahl, Annika; Lundin, Eva; Weiderpass, Elisabete; Vesper, Hubert; Riboli, Elio; Duell, Eric J

    2016-03-01

    Acrylamide, classified in 1994 by IARC as "probably carcinogenic to humans," was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI acrylamide or glycidamide were not associated with EC or type-I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort. © 2015 UICC.

  17. Biomarkers as prognostic factors in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Sławomir J Terlikowski

    2010-11-01

    Full Text Available Endometrial cancer is the most common gynecologic malignancy in more developed countries. Approximately 75% of cases are diagnosed at an early stage with a tumor confined to the uterine corpus. Although most patients are cured by surgery alone, about 15-20% with no signs of locally advanced or metastatic disease at primary treatment recurs, with limited responsiveness to systemic therapy. The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with a good prognosis and endometrioid histology and type II, associated with a poor prognosis and non-endometrioid histology. This review will focus primarily on the molecular biomarkers that have supported the dualistic model of endometrial carcinoma and help determine which patients would benefit from either adjuvant therapy or more aggressive primary treatment.

  18. Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

    African Journals Online (AJOL)

    Hossam Hassan Aly Hassan El Sokkary

    2013-10-31

    Oct 31, 2013 ... 1A endometrial carcinoma diagnosed preoperatively by pelvic ultrasonography and ... Endogenous risk factors include obesity, early menarche, ..... node resection in endometrioid corpus cancer: a study of 12,333 · patients.

  19. Metformin for endometrial hyperplasia: a Cochrane protocol

    Science.gov (United States)

    Clement, Naomi S; Oliver, Thomas R W; Shiwani, Hunain; Saner, Juliane R F; Mulvaney, Caroline A; Atiomo, William

    2016-01-01

    Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination

  20. Endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer: is screening necessary?

    Science.gov (United States)

    Lubián López, Daniel M; Orihuela López, Francisco; García-Berbel Molina, Lucía; Boza Novo, Patricia; Pozuelo Solís, Estrella; Menor Almagro, David; Comino Delgado, Rafael

    2014-04-01

    To evaluate the prevalence of endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer and to know if a baseline pretamoxifen endometrial assessment should be taken into consideration in these women at high risk. A cross-sectional study was carried out with 201 women with breast cancer. A diagnostic hysteroscopy was performed in all women. All formations suspected as polyps were removed. The prevalence of endometrial polyps was analyzed in all patients (n=182) and in premenopausal (n=49) and postmenopausal (n=118) women with estrogen receptor (ER) positive breast cancer (BC) according to their body mass index (BMI) and other risk factors. Hysteroscopic evaluation was possible in 182 cases (90.5%). Of the total of women, 160 (87.9%) were ER(+)BC patients, 133 (73.1%) postmenopausal women and 41.5% were obese (BMI≥30kg/m(2)). Endometrial polyps were found in 52 cases (28.5%) (3 cases of simple hyperplasia harbored within a polyp). In premenopausal patients with ER(+)BC, there were no statistical differences in endometrial polyps according to their BMI (22.3% in non-obese women vs 31.7% in obese) while in all patients (26.4% in non-obese vs 44.0% in obese) and in postmenopausal women with ER(+)BC (25.9% in non-obese vs 48.6% in obese) there were statistical differences. In all women the relative risk (RR) of endometrial polyps in obese patients was 2.24 (1.01-4.83), in obese postmenopausal women with ER(+)BC was 2.75 (1.01-7.40) and in obese premenopausal patients with ER(+)BC was 1.42 (0.80-3.29). Asymptomatic women with breast cancer have a high prevalence of baseline subclinical endometrial polyps and it is very high in obese postmenopausal patients with estrogen receptor positive breast cancer. Therefore, there may be a future role for baseline pretamoxifen screening of some sort for the obese asymptomatic postmenopausal patient, especially if they are elderly and ER positive. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    Science.gov (United States)

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  2. Uterine sarcoma Part II—Uterine endometrial stromal sarcoma: The TAG systematic review

    Directory of Open Access Journals (Sweden)

    Huann-Cheng Horng

    2016-08-01

    Full Text Available Endometrial stromal tumors are rare uterine tumors (<1%. Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS, and uterine undifferentiated sarcoma (UUS. This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS. Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.

  3. Human Endometrial CD98 Is Essential for Blastocyst Adhesion

    Science.gov (United States)

    Domínguez, Francisco; Simón, Carlos; Quiñonero, Alicia; Ramírez, Miguel Ángel; González-Muñoz, Elena; Burghardt, Hans; Cervero, Ana; Martínez, Sebastián; Pellicer, Antonio; Palacín, Manuel; Sánchez-Madrid, Francisco; Yáñez-Mó, María

    2010-01-01

    Background Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. Methods and Principal Findings Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. Conclusions These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window. PMID:20976164

  4. Human endometrial CD98 is essential for blastocyst adhesion.

    Directory of Open Access Journals (Sweden)

    Francisco Domínguez

    Full Text Available BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window.

  5. Association between visceral fat, IL-8 and endometrial cancer.

    Science.gov (United States)

    Ciortea, Razvan; Mihu, Dan; Mihu, Carmen Mihaela

    2014-01-01

    In endometrial cancer, visceral obesity, as a risk factor, is associated with a chronic inflammatory process, confirmed by the elevation of serum inflammatory markers in obese patients. The aim of the present study was to evaluate the correlation between visceral fat, assessed by ultrasonography, and the systemic levels of interleukin (IL)-8 in patients with endometrial cancer. This study also evaluated the usefulness of abdominal ultrasonography in assessing the visceral fat correlated with systemic inflammatory status, as an alternative method to identify patients at risk of endometrial cancer. The study was a case-control analysis including two groups of patients: Group I: 44 patients diagnosed with endometrial cancer; group II: 44 patients with no gynecological pathology. The diagnosis of endometrial cancer was performed following histopathological examination that evaluated the tissue material obtained through endometrial biopsy. These patients underwent ultrasound examination by which intraperitoneal fat was determined. IL-8 levels were determined for each patient. The Student's t-test was used for the comparison of the means and the Mann-Whitney test for rank comparison of two independent samples. In patients diagnosed with endometrial cancer, the visceral fat area evaluated by ultrasound was significantly larger (pendometrial cancer group were significantly elevated (pendometrial cancer.

  6. Is there any association between glutathione s-transferases m1 and glutathione s-transferases t1 gene polymorphisms and endometrial cancer risk? a meta-analysis

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    Xiuxiu Yin

    2017-01-01

    Full Text Available Epidemiological evidence on the association between genetic polymorphisms in glutathione S-transferases M1 (GSTM1 and T1 (GSTT1 genes and risk of endometrial cancer (EC has been inconsistent. In this meta-analysis, we seek to investigate the relationship between GSTM1 and GSTT1 polymorphisms and the risk of EC. We searched Medline, PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database to identify eligible studies. The pooled odds ratios (ORs with 95% confidence intervals (CIs for the association were determined using a fixed- or random-effect model. Tests for heterogeneity of the results and sensitivity analyses were performed. A total of six case–control studies were included in the final meta-analysis of GSTM1 (1293 cases and 2211 controls and GSTT1 (1286 cases and 2200 controls genotypes. Overall, GSTM1 null genotype was not significantly associated with an increased risk of EC (OR = 1.00, 95% CI = 0.76–1.30, P = 0.982. Similarly, for GSTT1 deletion genotype, we observed no association under the investigated model in the overall analysis (OR = 0.91, 95% CI = 0.64–1.30, P = 0.619. Subgroup analysis also showed no significant association between the GSTM1 null genotype and EC risk in hospital-based design (OR = 1.26, 95% CI = 0.93–1.71, P = 0.131 and no relationship between GSTT1 null genotype with EC risk in population-based design (OR = 1.18, 95% CI = 0.79–1.76, P = 0.407. However, GSTM1 null genotype contributed to an increased EC risk in population-based design (OR = 0.76, 95% CI = 0.60–0.97, P = 0.027, while null GSTT1 in hospital-based studies (OR = 0.70, 95% CI = 0.52–0.93, P = 0.015. The present meta-analysis suggested that GSTs genetic polymorphisms may not be involved in the etiology of EC. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null, and design-specific with the development of EC are needed to prove our findings.

  7. Genetics of Endometrial Cancers

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    Tsuyoshi Okuda

    2010-01-01

    Full Text Available Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.

  8. Presence of a polymicrobial endometrial biofilm in patients with bacterial vaginosis.

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    Alexander Swidsinski

    Full Text Available OBJECTIVE: To assess whether the bacterial vaginosis biofilm extends into the upper female genital tract. STUDY DESIGN: Endometrial samples obtained during curettage and fallopian tube samples obtained during salpingectomy were collected. Endometrial and fallopian tube samples were analyzed for the presence of bacteria with fluorescence-in-situ-hybridisation (FISH analysis with probes targeting bacterial vaginosis-associated and other bacteria. RESULTS: A structured polymicrobial Gardnerella vaginalis biofilm could be detected in part of the endometrial and fallopian tube specimens. Women with bacterial vaginosis had a 50.0% (95% CI 24.0-76.0 risk of presenting with an endometrial Gardnerella vaginalis biofilm. Pregnancy (AOR  = 41.5, 95% CI 5.0-341.9, p<0.001 and the presence of bacterial vaginosis (AOR  = 23.2, 95% CI 2.6-205.9, p<0.001 were highly predictive of the presence of uterine or fallopian bacterial colonisation when compared to non-pregnant women without bacterial vaginosis. CONCLUSION: Bacterial vaginosis is frequently associated with the presence of a structured polymicrobial Gardnerella vaginalis biofilm attached to the endometrium. This may have major implications for our understanding of the pathogenesis of adverse pregnancy outcome in association with bacterial vaginosis.

  9. Carcinogenic mechanisms of endometrial cancer: involvement of genetics and epigenetics.

    Science.gov (United States)

    Banno, Kouji; Yanokura, Megumi; Iida, Miho; Masuda, Kenta; Aoki, Daisuke

    2014-08-01

    Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, β-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  10. American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review.

    Science.gov (United States)

    Harkenrider, Matthew M; Block, Alec M; Alektiar, Kaled M; Gaffney, David K; Jones, Ellen; Klopp, Ann; Viswanathan, Akila N; Small, William

    This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the postoperative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early-stage endometrial cancer patients results in very low rates of vaginal recurrence (0-3.1%) with low rates of late toxicity which are primarily vaginal in nature. Post-Operative Radiation Therapy in Endometrial Cancer 2 (PORTEC-2) supports that VBT results in noninferior rates of vaginal recurrence compared to external beam radiotherapy for the treatment of high-intermediate risk patients. VBT as a boost after external beam radiotherapy, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians prefer joint decision making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multidisciplinary setting, and patients should be counseled properly regarding the risks and benefits of adjuvant therapy. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  11. Hysteroscopic Endometrial Resection in the Management of ...

    African Journals Online (AJOL)

    Background: Abnormal uterine bleeding (AUB) is a major health problem and it is a substantial cause of ill health in women. Medical treatment has a high failure rate and adverse effects. There are few published data on hysteroscopic endometrial resection (HER) in the management of patients with AUB. Objective: To ...

  12. Analysis of differential genetic expression in endometrial polyps of postmenopausal women.

    Science.gov (United States)

    Troncon, J K; Meola, J; Candido-Dos-Reis, F J; Poli-Neto, O B; Nogueira, A A; Rosa-E-Silva, J C

    2017-10-01

    To evaluate the expression of four genetic markers (PTEN, BCL2, MLH1, and CTNNB1), linked to endometrial carcinogenesis, in endometrial polyps of patients with and without postmenopausal bleeding in order to determine whether symptomatic endometrial polyps have a genetic phenotype similar to that of endometrial cancer. Samples were obtained hysteroscopically from endometrial polyps of postmenopausal patients, and the expression of genetic markers involved in the pathogenesis of endometrial cancer (PTEN, BCL2, MLH1, and CTNNB1) was analyzed. The expression of these markers was then compared between patients with and without symptoms, which was characterized as postmenopausal bleeding. Other clinical characteristics of the patients, such as duration of menopause, polyp size, presence of systemic hypertension, diabetes mellitus, and smoking habits were also analyzed. Samples from a total of 60 patients were obtained, as calculated for a test power of 0.80. No statistical differences (p > 0.05) were observed between the two groups concerning the expression of the studied endometrial cancer risk factor genes, or with regard to the clinical aspects evaluated. The study found no evidence that symptomatic endometrial polyps have a similar phenotype to type 1 endometrial cancer; further studies are needed in order to establish whether endometrial polyps are in fact true cancer precursors, or simply raise cancer incidence due to a detection bias.

  13. Oxidative stress in endometrial hyperplasia.

    Science.gov (United States)

    Gómez-Zubeldia, María Angeles; Bazo, Ascensión Pérez; Gabarre, Juan José Arbués; Nogales, Agustín García; Palomino, José Carlos Millán

    2008-01-01

    Reactive oxygen species seem to be involved in the onset and promotion of carcinogenesis. In 80% of cases of endometrial adenocarcinoma type I, a clear association exists with endometrial hyperplasia, which is considered a key factor in the endometrial oncological spectrum. The presence or absence of atypical cells determines oncological potential. This study explored the behavior of oxidative stress (catalase and malondialdehyde) in endometrial hyperplasia (with or without atypical cells) by comparing it with the oxidative stress existing in both the proliferative and secretory phases. Endometrial specimens from 55 women were used, 32 of which were histologically diagnosed as physiological (17 proliferative and 15 secretory endometria) and 23 as endometrial hyperplasia (18 nonatypical and 5 atypical endometrial hyperplasia). Significant differences were found in the malondialdehyde variable between the proliferative endometrium and the endometrium with atypical hyperplasia (P = 0.0208) and between both types of endometrial hyperplasia (P = 0.0441). The other comparisons were not statistically significant. No changes in catalase activity were observed. Our findings seem to suggest that the presence of atypical cells in endometrial hyperplasia induces a reduction in lipid peroxidation, which could permit survival and growth of these cells. This possible decrease in lipid peroxidation does not seem to be mediated by an increase in endometrial catalase activity.

  14. Trends in the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer, 1990–2010

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    Hachisuga T

    2012-05-01

    Full Text Available Taisei Honda, Rie Urabe, Tomoko Kurita, Seiji Kagami, Toshinori Kawagoe, Naoyuki Toki, Yusuke Matsuura, Toru HachisugaDepartment of Obstetrics and Gynecology, University of Occupational and Environmental Health School of Medicine, Yahatanishi-ku, Kitakyushu, JapanObjective: Over the past 20 years, the incidence of endometrial cancer has increased remarkably in Japan. The number of elderly females has also increased within the population of Japan. We examined the impact of advanced age on the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer.Methods: Data were collected from 319 surgically treated Japanese females with endometrial cancer from the files of the University Hospital of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan, between 1990 and 2010. χ2 tests were performed to evaluate the trends in the variables between two decades (A: 116 cases from 1990–2000 and (B: 203 cases in 2001–2010. The histological subtypes were also evaluated based on the immunohistochemical expressions of p53, estrogen receptor, and Ki-67.Results: The mean ages ± standard deviation in the decade A group and the decade B group were 57.5 years ± 9.7 years and 61.0 years ± 11.3 years, respectively (P < 0.02. There was an increase in the proportion of patients aged 70 years or older and of high-risk histological tumors including serous carcinoma, clear cell carcinoma, and carcinosarcoma (decade A group and decade B group: 9.5% vs 27.6%, P < 0.001, 10.4% vs 21.6%, P = 0.01, respectively, while the advanced surgical stage (III and IV, obesity (≥25 of body mass index, and nulliparity of the decade A group and decade B group were 23.3% vs 29.1%, P = 0.30, 28.4% vs 33.0%, P = 0.40, and 19.0% vs 21.2%, P = 0.66, respectively. The cancer-specific survival rates in the decade A group and the decade B group were 78.6% and 77.6%, respectively (P = 0.93.Conclusion: The increase in number of elderly

  15. [Prognostic factors in diagnosed endometrial cancers determining the type of radical surgery].

    Science.gov (United States)

    Ivanov, S; Tomov, S

    2009-01-01

    Our aim was to research and evaluate for 10 years period the most important prognostic factors, related and determining the choice of suitable type of radical surgical treatment. It was performed in diagnosed endometrial cancer patients. We researched 460 patients with endometrial cancer for 10 years period. All of them were operated by radical programme. We evaluated the following prognostic factors: stage, age, histological type, tumor grading, invasion of the tumor in myometrium, tumor volume, peritoneal cytology, LVSI, hormonal receptor status, nuclear grading, DNA--ploidy, the extent of the lymph node dissection (number of lymph nodes) and specific genetic alterations connected with endometrial cancers. The surgical determined stage was the most important prognostic factor. The age was independent factor. The histological type was very important prognostic factor--the endometrioid cancers were with better survival rate (89%) in comparison with the rare papillary-serous and clear cell cancers (30%). The tumor grading and myometrical invasion had a very important prognostic significance. When the patients were with grade 3 and infiltration in the outer third of myometrium--the positive pelvic lymph nodes were 30% and the paraaortal--20%. The tumor volume according to us is an independent prognostic factor. When the diameter of the tumor was less than 2 cm--the metastases in the lymph nodes were 3% and when the diameter was more than 2 cm--the metastases were 18%. If the tumor volume occupied the whole endometrial cavity and invasion in myometrium was deep, we had 40% metastases in the lymph nodes. The peritoneal cytology had a relative risk. The LVSI was independent prognostic factor. The ER and PR were independent prognostic factors. The nuclear grading--according to our results is a significant prognostic factor. The aneuploidy was the strongest independent factor for bad survival after age and stage. The extent (the volume) of the lymph node dissection was

  16. Therapeutic analysis of high-dose-rate {sup 192}Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu; Donnelly, Eric D.; Strauss, Jonathan B. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois 60611 (United States); Qi, Yujin [Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2016-01-15

    Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model was used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0){sup 4} to (13

  17. Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations.

    Science.gov (United States)

    Hoang, Lien; Chiang, Sarah; Lee, Cheng-Han

    2018-02-01

    Our understanding of endometrial stromal sarcomas has evolved dramatically since their earliest descriptions from over a century ago. Initial studies focused on establishing the relationship between histological appearances of endometrial stromal sarcomas and their clinical outcomes. Studies performed in the last decade have uncovered several recurrent cytogenetic aberrations occurring in low- and high-grade endometrial stromal sarcomas. Low-grade endometrial stromal sarcomas bear close histopathological resemblance to proliferative-type endometrial stroma, and approximately half harbour t(7;17)(p15;q21) resulting in JAZF1-SUZ12 gene fusion. Less common JAZF1-PHF1, EPC1-PHF1, MEAF6-PHF1, and MBTD1-CXorf67 fusions have also been reported. The term 'high-grade endometrial stromal sarcoma' was recently re-introduced in the classification of endometrial stromal tumours after the discovery of t(10;17)(q22;p13) resulting in YWHAE-NUTM2A/B fusion and is associated with distinct morphological characteristics. This review highlights the evolution of endometrial stromal sarcoma classification schemes over time and describes the salient clinicopathological and molecular features of endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. It also describes the recent characterisation of endometrial stromal sarcoma with t(X;22)(p11;q13) resulting in ZC3H7B-BCOR fusion, a noteworthy entity due to its close histological resemblance to myxoid leiomyosarcoma. We also provide insights into common challenging scenarios encountered when assessing endometrial stromal lesions in daily surgical pathology practice. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  18. Associations between etiologic factors and mortality after endometrial cancer diagnosis: the NRG Oncology/Gynecologic Oncology Group 210 trial.

    Science.gov (United States)

    Felix, Ashley S; Scott McMeekin, D; Mutch, David; Walker, Joan L; Creasman, William T; Cohn, David E; Ali, Shamshad; Moore, Richard G; Downs, Levi S; Ioffe, Olga B; Park, Kay J; Sherman, Mark E; Brinton, Louise A

    2015-10-01

    Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial. Prior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators. Median follow-up was 60months after enrollment (range: 1day-118months). Among 4609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR=1.04, 95% CI=1.01-1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR=2.29, 95% CI=1.06-4.98, P-trend=0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR=1.05, 95% CI=1.02-1.07 per year, P-trendendometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR=0.55, 95% CI=0.36-0.82) and carcinosarcoma cases (HR=2.01, 95% CI=1.00-4.05). Several endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis. ClinicalTrials.gov Identifier: NCT00340808. Published by Elsevier Inc.

  19. Robotic infrarenal paraaortic and pelvic nodal staging for endometrial cancer: feasibility and lymphatic complications.

    Science.gov (United States)

    Geppert, Barbara; Persson, Jan

    2015-10-01

    This study was designed to evaluate the feasibility and lymphatic complications of robotic pelvic and infrarenal paraaortic lymphadenectomy in endometrial cancer patients. All patients diagnosed with high risk endometrial cancer during the study period were identified (n = 212). Clinical prospective data, with reassessment of lymphatic complications, was analysed for all cases (n = 140) planned for a complete robotic nodal staging. The outcome measures were: success rate of infrarenal paraaortic lymphadenectomy, the rate of lymphatic complications and factors associated with nodal yield. Of the 212 women, an open or restricted robotic procedure was performed in 57 women (27%) and no operation in 15 (7%), the latter due to disseminated disease or comorbidity. In 140 women (66%) in whom staging was intended, the lymphadenectomy included the infrarenal area in 70%, was restricted to the inframesenteric area in 21% and aborted or incomplete in 9%. The median number of paraaortic nodes was 10 (range 2-39). An unsuccessful staging was associated with high BMI and the surgeon's inexperience. At 1 year, three patients (2%) had developed a grade two lower limb lymphedema. Eleven women (8%) demonstrated pelvic lymphocysts; seven (64%) resolved spontaneously. Only one paraaortic lymphocyst was found; this required drainage. No cases of chylous ascites occurred. An infrarenal robotic paraaortic lymphadenectomy is feasible in 70% of high risk endometrial cancer cases when intended (88% in non-obese patients operated by experienced surgeons), but is restricted in obese patients and by surgeon's inexperience. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  20. Robotics in Endometrial Cancer Care

    Directory of Open Access Journals (Sweden)

    Joseph Ng

    2013-11-01

    Full Text Available Endometrial cancer is the most common gynecological cancer in women in most of the developed world. The majority of these women with endometrial cancer will be unaffected by their disease. The challenge therefore is for surgical treatment not to be worse than the disease. Robotics has changed the way that we care for women living with endometrial cancer by making low-impact surgical treatment available to more women than was previously possible.

  1. Endometrial polyp or neoplasia? A case-control study in women with polyps at ultrasound.

    Science.gov (United States)

    Gambadauro, P; Martínez-Maestre, M Á; Schneider, J; Torrejón, R

    2015-06-01

    To identify factors associated with endometrial neoplasia in women diagnosed with endometrial polyp at transvaginal ultrasound. Within a population of 1390 consecutive patients undergoing hysteroscopy following an ultrasonographic diagnosis of polyps, we compared the cases with a final diagnosis of endometrial neoplasia with controls with benign endometrial polyps. The controls were selected randomly in a ratio of 4 : 1 (controls : cases). Bivariate statistical analysis and multiple logistic regression were used to measure the association between various variables and endometrial neoplasia. Sixteen cases of endometrial neoplasia were compared to 64 controls with confirmed benign endometrial polyps. All cases of neoplasia were among symptomatic women, while 40.62% of women with benign polyps had been referred to hysteroscopy after a routine ultrasound and were asymptomatic. Women with endometrial neoplasia were significantly older (mean age 64.19 ± 9.382 vs. 52.03 ± 9.846 years; p neoplasia were postmenopausal status and bleeding as a main symptom. At multivariate analysis with logistic regression, the only factors showing a statistically significant association with endometrial neoplasia were older age (odds ratio 1.102; 95% confidence interval 1.015-1.198) and bleeding (odds ratio 13.7; 95% confidence interval 1.486-126.278). When polyps are diagnosed at ultrasound, bleeding and an older age are independently associated with endometrial neoplasia. A significant proportion of asymptomatic women is referred to hysteroscopy because of a polyp seen at routine ultrasound, although malignancy is highly unlikely in these cases.

  2. Robotic surgical staging for endometrial and cervical cancers in medically ill patients.

    Science.gov (United States)

    Siesto, Gabriele; Ornaghi, Sara; Iedà, Nicoletta; Vitobello, Domenico

    2013-06-01

    Patients with high anesthesiological risk due to old age, obesity and severe co-morbidities alone or in combination are considered as poor candidates for extensive surgical staging procedures, especially if through minimally invasive approach. We aimed to evaluate the feasibility and safety of robotic surgical staging of endometrial and cervical cancers in the medically ill patient. Between 07-2007 and 12-2012, consecutive patients scheduled for staging for endometrial or cervical cancer were directed towards robotic staging and divided into two groups according to their starting score in the American Society for Anaesthesiologists (ASA): Group 1 (ASA 1-2) and Group 2 (ASA ≥3). Overall, 169 (71.9%) patients had ASA 1-2 whereas 66 (28.1%) had ASA ≥3. ASA ≥3 were older (pobesity (2.4% vs 31.8%; pcervical cancers also in this more vulnerable group of patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer

    DEFF Research Database (Denmark)

    Verdoodt, F.; Kjaer, S. K.; Friis, S.

    2017-01-01

    Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...

  4. Endometrial Adenocarcinoma and Mucocele of the Appendix: An Unusual Coexistence

    Directory of Open Access Journals (Sweden)

    Ioannis Kalogiannidis

    2013-01-01

    Full Text Available Appendiceal mucocele is a rare clinical entity, which is however quite often associated with mucinous ovarian tumor. The coexistence of mucinous cystadenoma of the appendix and endometrial adenocarcinoma has not been reported before. A 49-year-old woman presented to our clinic with postmenopausal bleeding and no other symptom. Endometrial biopsy revealed endometrial adenocarcinoma of endometrioid type (grade I. Preoperative CT scanning revealed an appendiceal mucocele, and a colonoscopy confirmed the diagnosis. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and appendectomy. The final histopathological examination showed a mucinous cystadenoma of the appendix and confirmed the diagnosis of endometrioid endometrial adenocarcinoma. The coexistence of appendiceal mucocele and female genital tract pathology is rare. However, gynecologists should keep a high level of suspicion for such possible coexistence. Both the diagnostic approach and the therapeutic management should be multidisciplinary, most importantly with the involvement of general surgeons.

  5. Endometrial cancers in mutation carriers from hereditary breast ovarian cancer syndrome kindreds: report from the Creighton University Hereditary Cancer Registry with review of the implications.

    Science.gov (United States)

    Casey, Murray Joseph; Bewtra, Chhanda; Lynch, Henry T; Snyder, Carrie L; Stacey, Mark

    2015-05-01

    The aim of this study was to categorize and report endometrial cancers in mutation carriers from hereditary breast ovarian cancer families. Our Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers linked to mutations in BRCA1 or BRCA2. Invasive cancers were registered in 101 mutation carriers with complete pathology reports. Efforts were made to secure diagnostic surgical pathology tissues for review. All records and available diagnostic slides were meticulously studied, and primary cancers were classified. Eight malignancies were classified as primary endometrial cancers. Five of these were low- or intermediate-grade endometrioid carcinomas, and 3 were pure serous carcinomas or contained serous carcinoma elements mixed with high-grade endometrioid carcinoma. Breast cancers were diagnosed in 5 patients before and in 1 patient after endometrial carcinoma. Three endometrioid carcinomas were preceded by estrogen treatment, 2 for many years and the other for only 2 months, and 2 of the patients with serous carcinoma had been treated with tamoxifen. The finding that 8 of gynecologic and peritoneal cancers in 101 mutation carriers were endometrial cancers with a smaller proportion of endometrioid carcinomas than reported in general populations is added to the current controversial literature on endometrial cancer, particularly regarding serous carcinomas, in hereditary breast ovarian cancer syndrome. Well-designed prospective programs for standardized surgical and pathologic handling, processing, and reporting are essential for working out the pathogenesis, true risks, and best management of this disease in carriers of deleterious BRCA1 and BRCA2 germline mutations.

  6. Pólipos endometriais Endometrial polyps

    Directory of Open Access Journals (Sweden)

    Antonio Alberto Nogueira

    2005-05-01

    Full Text Available Os pólipos endometriais são lesões benignas, com baixo potencial de malignização. No período reprodutivo seu diagnóstico é obtido nas pacientes sintomáticas, com sangramento uterino anormal ou infertilidade. Na pós-menopausa em sua maioria são assintomáticos, podendo estar associados a sangramento anormal em torno de um terço dos casos. São mais freqüentes na pós-menopausa e os fatores de risco para câncer de endométrio não têm sido associados da mesma maneira, como de risco para pólipos endometriais, embora sejam hormônio-dependentes, como nas pacientes usuárias do tamoxifeno, por exemplo. Seu diagnóstico definitivo é realizado pelo exame histológico com amostra obtida de maneira mais eficiente por biópsia dirigida por meio da histeroscopia, assim como seu tratamento mais efetivo é a ressecção histeroscópica. Pólipos podem apresentar recorrência após tratamento. A polipectomia é altamente satisfatória na pós-menopausa, tem menor taxa de sucesso em mulheres sintomáticas no período reprodutivo e melhora as taxas de fertilidade em mulheres inférteis.Endometrial polyps are benign lesions, with a low potential of malignancy. In the reproductive period their diagnosis is established in symptomatic patients with abnormal uterine bleeding or infertility. Postmenopausal women are mostly asymptomatic but in approximately one third of the cases there is an association with abnormal bleeding. They are more frequent after the menopause and risk factors of cancer of the endometrium have not been associated in the same way as risk for endometrial polyps, although they are hormone-dependent as in patients in use of tamoxifen, for instance. Their definitive diagnosis is established by hysteroscopy-guided biopsy and their most effective treatment is hysteroscopic resection. Polyps may recur after treatment. Polypectomy is highly satisfactory after the menopause, is less successful in symptomatic women in the reproductive

  7. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    Energy Technology Data Exchange (ETDEWEB)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  8. Local recruitment experience in a study comparing the effectiveness of a low glycaemic index diet with a low calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Atiomo, William; Read, Anna; Golding, Mary; Silcocks, Paul; Razali, Nuguelis; Sarkar, Sabitabrata; Hardiman, Paul; Thornton, Jim

    2009-09-01

    Feasibility of a clinical-trial comparing a low-glycaemic diet with a low-calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with PCOS. A pilot Randomised-Controlled-Trial using different recruitment strategies. A University Hospital in the United Kingdom. Women seen at specialist gynaecology clinics over a 12 month period in one University Hospital, and women self identified through a website and posters. Potential recruits were assessed for eligibility, gave informed consent, randomised, treated and assessed as in the definitive trial. Eligibility and recruitment rates, compliance with the allocated diet for 6 months and with clinical assessments, blood tests, pelvic ultrasound scans and endometrial biopsies. 1433 new and 2598 follow up patients were seen in 153 gynaecology clinics for over 12 months. 441 (11%) potentially eligible women were identified, 19 (0.4%) of whom met the trial entry criteria. Eleven consented to take part, of which 8 (73%) completed the study. Planned future trials on over-weight women with PCOS should be multicentre and should incorporate primary care. This data will help other researchers plan and calculate the sample size and potential recruitment rates in future clinical trials in PCOS. The results will also be useful for inclusion in future meta-analyses.

  9. Lymph Node Assessment in Endometrial Cancer: Towards Personalized Medicine

    Directory of Open Access Journals (Sweden)

    Fabien Vidal

    2013-01-01

    Full Text Available Endometrial cancer (EC is the most common malignancy of the female reproductive tract and is increasing in incidence. Lymphovascular invasion and lymph node (LN status are strong predictive factors of recurrence. Therefore, the determination of the nodal status of patients is mandatory to optimally tailor adjuvant therapies and reduce local and distant recurrences. Imaging modalities do not yet allow accurate lymph node staging; thus pelvic and aortic lymphadenectomies remain standard staging procedures. The clinical data accumulated recently allow us to define low- and high-risk patients based on pre- or peroperative findings that will allow the clinician to stratify the patients for their need of lymphadenectomies. More recently, several groups have been introducing sentinel node mapping with promising results as an alternative to complete lymphadenectomy. Finally, the use of peroperative algorithm for risk determination could improve patient's staging with a reduction of lymphadenectomy-related morbidity.

  10. Spontaneous conception in 40-year-old infertile woman with polycystic ovaries after complete reversal of endometrial intraepithelial neoplasia: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Swati Verma

    2016-01-01

    Full Text Available We report a case of polycystic ovary syndrome and prolonged infertility in which endometrial intraepithelial neoplasia was reversed with high dose progesterone therapy. Spontaneous conception after failure of assisted reproductive techniques highlights the role of endometrial receptivity.

  11. Ornithine decarboxylase as a therapeutic target for endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Hong Im Kim

    Full Text Available Ornithine Decarboxylase (ODC a key enzyme in polyamine biosynthesis is often overexpressed in cancers and contributes to polyamine-induced cell proliferation. We noted ubiquitous expression of ODC1 in our published endometrial cancer gene array data and confirmed this in the cancer genome atlas (TCGA with highest expression in non-endometrioid, high grade, and copy number high cancers, which have the worst clinical outcomes. ODC1 expression was associated with worse overall survival and increased recurrence in three endometrial cancer gene expression datasets. Importantly, we confirmed these findings using quantitative real-time polymerase chain reaction (qRT-PCR in a validation cohort of 60 endometrial cancers and found that endometrial cancers with elevated ODC1 had significantly shorter recurrence-free intervals (KM log-rank p = 0.0312, Wald test p = 5.59e-05. Difluoromethylornithine (DFMO a specific inhibitor of ODC significantly reduced cell proliferation, cell viability, and colony formation in cell line models derived from undifferentiated, endometrioid, serous, carcinosarcoma (mixed mesodermal tumor; MMT and clear cell endometrial cancers. DFMO also significantly reduced human endometrial cancer ACI-98 tumor burden in mice compared to controls (p = 0.0023. ODC-regulated polyamines (putrescine [Put] and/or spermidine [Spd] known activators of cell proliferation were strongly decreased in response to DFMO, in both tumor tissue ([Put] (p = 0.0006, [Spd] (p<0.0001 and blood plasma ([Put] (p<0.0001, [Spd] (p = 0.0049 of treated mice. Our study indicates that some endometrial cancers appear particularly sensitive to DFMO and that the polyamine pathway in endometrial cancers in general and specifically those most likely to suffer adverse clinical outcomes could be targeted for effective treatment, chemoprevention or chemoprevention of recurrence.

  12. 21 CFR 884.1100 - Endometrial brush.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food... Endometrial brush. (a) Identification. An endometrial brush is a device designed to remove samples of the... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...

  13. 21 CFR 884.1185 - Endometrial washer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food... Endometrial washer. (a) Identification. An endometrial washer is a device used to remove materials from the... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification...

  14. Hyperinsulinemia-induced PAX6 expression promotes endometrial epithelial cell proliferation via negatively modulating p27 signaling.

    Science.gov (United States)

    Zheng, Xue-Rong; Pan, Xia; Zhang, Jin; Cao, Xin

    2018-01-01

    Polycystic ovarian syndrome (PCOS) is thought to involve hyperinsulinism (insulin resistance, IR) and high prevalence of endometrial epithelial hyperplasia, but how these two pathologies are synergistically regulated in endometrial epithelial cells remains largely unknown. Here, we report a key role for the transcription factor PAX6 in the modulation of PCOS-induced endometrial epithelial proliferation. PAX6 was significantly induced in the endometrial tissues from PCOS patients, and this induction, regulated upstream by high levels of insulin, was closely correlated to the pathogenesis of IR in endometrial epithelial cells. Overexpression of the exogenous PAX6 potentiated the insulin-elicited accumulation of S phase in endometrial epithelial cells and thereby promoted endometrial epithelial proliferation. In parallel, by using luciferase reporter and ChIP assay, we found that PAX6 directly bound to the promoter of CDKN1B gene (the gene encoding p27 protein, a negative regulator of cell cycle) and inhibited CDKN1B transcription in the insulin-stimulated endometrial epithelial cells. We conclude that excessive PAX6 expression in insulin-challenged endometrial epithelial cells may contribute to the uncontrollable endometrial epithelial proliferation. Our results also provide a mechanistic explanation for the functional link between hyperinsulinemia and p27 loss in the pathogenesis of endometrial epithelial hyperplasia in PCOS patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Endometrial Adenocarcinoma with Concomitant Left Atrial Myxoma

    Directory of Open Access Journals (Sweden)

    Lisa N. Abaid

    2009-08-01

    Full Text Available Background: Atrial myxomas are the most common primary heart tumors and predominantly considered to be benign lesions. Case Study: We report a case involving a 77-year-old woman who presented with a pelvic mass. She was found to have a primary endometrial cancer and primary lung cancer with concomitant metastatic adrenal gland and mesenteric lesions. Her prior medical history also included an untreated 4.0 × 2.0-cm left atrial myxoma which was identified on CT scan during the workup of her pelvic mass. Results: A clinical decision was made to proceed with surgery for the pelvic mass with a subsequent recommendation for left atrial mass resection. Currently, the patient is scheduled to begin chemotherapy for primary lung cancer. Conclusion: The reported incidence of uterine cancer and a concurrent atrial myxoma is very rare. Consequently, the manner and timing in which treatment should be provided is imprecise. In the present case, the risk for cardiac complications was high, but given the presence of a partial bowel obstruction and the need to diagnose the primary site of her metastatic malignancy, the decision was made to proceed with exploratory abdominal surgery.

  16. Prospective evaluation of abnormal glucose metabolism and insulin resistance in patients with atypical endometrial hyperplasia and endometrial cancer.

    Science.gov (United States)

    Mitsuhashi, Akira; Uehara, Takashi; Hanawa, Shinsuke; Shozu, Makio

    2017-05-01

    Obesity and diabetes (DM) are known to increase the risk of endometrial cancer (EC). However, little is known about the prevalence of abnormal glucose metabolism and insulin resistance (IR) in EC patients. We aimed to evaluate the prevalence of abnormal glucose metabolism and IR in EC patients. We prospectively enrolled atypical endometrial hyperplasia (AEH) and EC patients who had received planned treatment at Chiba University Hospital, Japan. All patients, except those with a confirmed diagnosis of DM, underwent the 75-g oral glucose tolerance test (OGTT) before treatment. We evaluated the prevalence of obesity, defined as body mass index (BMI) ≥25, IR, abnormal glucose metabolism, and the associations between these three factors and the clinical characteristics of AEH and EC patients. We enrolled 279 patients from April 2009 to March 2015. Of these, 56 had a confirmed diagnosis of DM. Abnormal OGTT results, including impaired fasting glucose (n = 7), impaired glucose tolerance (n = 69), and newly identified DM (n = 33), were noted in 109 patients. Obesity, IR, and abnormal glucose metabolism were observed in 49.8, 51.6, and 59.1% of patients, respectively. Abnormal glucose metabolism was significantly associated with age (P obesity were highly prevalent in patients with AEH and EC. These results indicate that physicians should consider a patient's metabolic status in the postoperative management of AEH and EC patients.

  17. Disparities in reproductive outcomes according to the endometrial preparation protocol in frozen embryo transfer : The risk of early pregnancy loss in frozen embryo transfer cycles.

    Science.gov (United States)

    Hatoum, I; Bellon, L; Swierkowski, N; Ouazana, M; Bouba, S; Fathallah, K; Paillusson, B; Bailly, M; Boitrelle, F; Alter, L; Bergère, M; Selva, J; Wainer, R

    2017-11-06

    The purpose of this study was to determine the effect of stimulated and artificial endometrial preparation protocols on reproductive outcomes in frozen embryo transfer (FET) cycles. We performed a retrospective study of 1926 FET cycles over a 3.5-year period in the Fertility Unit at a University Hospital. Stimulated and artificial protocols were used for endometrial preparation. The embryos for FET were obtained from either in vitro fertilization or intracytoplasmic sperm injection cycles. Live birth rate and early pregnancy loss rates were retrospectively compared. In artificial protocols, oral or vaginal administration of oestradiol 2 mg two or three times a day was followed by vaginal supplementation with progesterone 200 mg two or three times a day. In stimulated protocols, recombinant follicle-stimulating hormone was administered from day 4 onward. Vaginal ultrasound was used for endometrial and ovarian monitoring. A pregnancy test was performed 14 days after FET. If it was positive, oestradiol and progesterone were administered up until the 12th week of gestation in artificial cycles. We defined early pregnancy losses as biochemical pregnancies (preclinical losses) and miscarriages. Data on 865 artificial cycles (45% of the total) and 1061 stimulated cycles (55%) were collected. Early pregnancy loss rate was significantly lower for stimulated cycles (34.2%) than for artificial cycles (56.9%), and the live birth rate was significantly higher for stimulated cycles (59.7%) than for artificial cycles (29.1%). In frozen embryo transfer, artificial cycles were associated with more early pregnancy loss and lower live birth rate than stimulated cycles.

  18. SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading.

    Science.gov (United States)

    Pityński, Kazimierz; Banas, Tomasz; Pietrus, Milosz; Milian-Ciesielska, Katarzyna; Ludwin, Artur; Okon, Krzysztof

    2015-01-01

    Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.

  19. Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women.

    Science.gov (United States)

    Holden, Emily C; Dodge, Laura E; Sneeringer, Rita; Moragianni, Vasiliki A; Penzias, Alan S; Hacker, Michele R

    2017-06-18

    Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

  20. Clinicopathologic characteristics of double primary endometrial and colorectal cancers in a single institution.

    Science.gov (United States)

    Lee, Hyun J; Choi, Min C; Jang, Ja-Hyun; Jung, Sang G; Park, Hyun; Joo, Won D; Kim, Tae H; Lee, Chan; Lee, Je H

    2018-02-14

    To investigate the clinicopathologic and genetic correlations between double primary endometrial and colorectal cancer related to Lynch syndrome and to analyze germline mutations in mismatch repair genes in endometrial cancer patients in Korea. Thirteen patients diagnosed with pathologically endometrial and colorectal cancer between January 2005 and November 2016 in a single institution were enrolled in the study. The medical records were retrospectively analyzed. The genetic mutational information of endometrial cancer in Korea was retrieved from the literature review. Endometrial cancer was diagnosed first in eight (62%) patients, and one patient was diagnosed with colorectal cancer first. Endometrioid adenocarcinoma was reported in 10 of 13 (77%) endometrial cancer patients. Endometrial cancer was found at the low uterine segment in three patients. Three of four patients had high microsatellite instability. The loss of mismatch repair proteins was confirmed in 7 of 11 cases using immunohistochemistry. Four patients fulfilled clinical criteria based on a family history of cancer. Overall, the incidence of suspected Lynch syndrome was 77% (10/13). Four of them underwent genetic testing and three were found to have a pathogenic germline mutation. A possible founder mutation, c.1757_1758insC in MLH1, was observed in 21 germline mutation information from literature review. The present study describes the clinicopathologic data of double primary endometrial and colorectal cancer patients and supports that these patients should undergo closed approach for Lynch syndrome. Moreover, a possible founder mutation in Korean endometrial cancer patients was identified. © 2018 Japan Society of Obstetrics and Gynecology.

  1. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Nead, Kevin T; Sharp, Stephen J; Thompson, Deborah J; Painter, Jodie N; Savage, David B; Semple, Robert K; Barker, Adam; Perry, John R B; Attia, John; Dunning, Alison M; Easton, Douglas F; Holliday, Elizabeth; Lotta, Luca A; O'Mara, Tracy; McEvoy, Mark; Pharoah, Paul D P; Scott, Rodney J; Spurdle, Amanda B; Langenberg, Claudia; Wareham, Nicholas J; Scott, Robert A

    2015-09-01

    Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10(-6)). This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. © The Author 2015. Published by Oxford University Press.

  2. Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life.

    Science.gov (United States)

    Modesitt, Susan C; Hallowell, Peter T; Slack-Davis, Jill K; Michalek, Ryan D; Atkins, Kristen A; Kelley, Sarah L; Arapovic, Sanja; Shupnik, Margaret A; Hoehn, Kyle

    2015-08-01

    The study objectives were to determine baseline endometrial histology in morbidly obese women undergoing bariatric surgery and to assess the surgical intervention's impact on serum metabolic parameters, quality of life (QOL), and weight. Women undergoing bariatric surgery were enrolled. Demographic and clinicopathologic data, serum, and endometrium (if no prior hysterectomy) were collected preoperatively and serum collected postoperatively. Serum global biochemical data were assessed pre/postoperatively. Welch's two sample t-tests and paired t-tests were used to identify significant differences. Mean age of the 71 women enrolled was 44.2 years, mean body mass index (BMI) was 50.9 kg/m(2), and mean weight loss was 45.7 kg. Endometrial biopsy results: proliferative (13/30; 43%), insufficient (8/30; 27%), secretory (6/30; 20%) and hyperplasia (3/30; 10%-1 complex atypical, 2 simple). QOL data showed significant improvement in physical component scores (PCS means 33.9 vs. 47.2 before/after surgery; pcancer protective effects of bariatric surgery may be due to other mechanisms other than simply hormonal changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Infant Feeding and the Incidence of Endometrial Cancer

    Science.gov (United States)

    Xue, Fei; Hilakivi-Clarke, Leena A.; Maxwell, G. Larry; Hankinson, Susan E.; Michels, Karin B.

    2010-01-01

    Biological mechanisms could support both an inverse and a direct association between exposure to breast milk in infancy and the risk of cancer. Having been breast-fed has been investigated in relation to the risk of breast and other cancer sites, and conflicting results have been reported. The association between infant feeding and the risk of endometrial cancer has not been explored. From 1976 to 2004, we followed 74,757 cancer-free participants in the Nurses’ Health Study who had not undergone hysterectomy. Information on infant feeding was self-reported by study participants. A total of 708 incident cases of endometrial cancer were diagnosed during follow-up. After adjusting for age, family history of endometrial cancer, birth weight, premature birth, and birth order, the incidence of endometrial cancer was not associated with ever having been breast-fed (hazards ratio, 0.94; 95% confidence interval, 0.79–1.11) or duration of having been breast-fed [hazards ratio (95% confidence interval): 1.11 (0.80–1.54), 0.84 (0.62–1.13), 1.02 (0.79–1.31), respectively, for ≤3, 4–8, and ≥9 months of having been breastfed; P for trend = 0.88]. There was no significant effect modification by menopausal status, anthropometric factors (somatotype at age 5 or 10 years, body mass index at age 18 years, or current body mass index), or by other early-life exposures (birth weight, premature birth or exposure to parental smoking in childhood). Additional adjustment for adulthood risk factors of endometrial cancer did not materially change the results. Having been breast-fed was not associated with the incidence of endometrial cancer in this cohort, but statistical power for analyses restricted to premenopausal women was limited. PMID:18541614

  4. Chemopreventive effects of metformin on obesity-associated endometrial proliferation.

    Science.gov (United States)

    Zhang, Qian; Celestino, Joseph; Schmandt, Rosemarie; McCampbell, Adrienne S; Urbauer, Diana L; Meyer, Larissa A; Burzawa, Jennifer K; Huang, Marilyn; Yates, Melinda S; Iglesias, David; Broaddus, Russell R; Lu, Karen H

    2013-07-01

    Obesity is a significant contributing factor to endometrial cancer risk. We previously demonstrated that estrogen-induced endometrial proliferation is enhanced in the context of hyperinsulinemia and insulin resistance. In this study, we investigate whether pharmacologic agents that modulate insulin sensitivity or normalize insulin levels will diminish the proliferative response to estrogen. Zucker fa/fa obese rats and lean controls were used as models of hyperinsulinemia and insulin resistance. Insulin levels were depleted in ovariectomized rats following treatment with streptozotocin, or modulated by metformin treatment. The number of BrdU-incorporated cells, estrogen-dependent proliferative and antiproliferative gene expression, and activation of mTOR and ERK1/2 MAPK signaling were studied. A rat normal endometrial cell line RENE1 was used to evaluate the direct effects of metformin on endometrial cell proliferation and gene expression in vitro. Streptozotocin lowered circulating insulin levels in obese rats and decreased the number of BrdU-labeled endometrial cells even in the presence of exogenous estrogen. Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRβ/IGF1R) and ERK1/2. In vitro studies indicated metformin inhibited RENE1 proliferation in a dose-dependent manner. These findings suggest that drugs that modulate insulin sensitivity, such as metformin, hinder estrogen-mediated endometrial proliferation. Therefore, these drugs may be clinically useful for the prevention of endometrial cancer in obese women. Copyright © 2013 Mosby, Inc. All rights reserved.

  5. Detection of endometrial and subendometrial vasculature on the day of embryo transfer and prediction of pregnancy during fresh in vitro fertilization cycles

    Directory of Open Access Journals (Sweden)

    Ari Kim

    2014-09-01

    Conclusion: Three dimensional PD-US was a useful and effective method for assessing endometrial blood flow in IVF cycles. Good endometrial blood flow on the day of embryo transfer might be associated with high pregnancy success with a GnRH long protocol, because this is indicative of endometrial receptivity in fresh IVF cycles.

  6. Endometrial abnormalities on transvaginal ultrasonography and histopathology in women after quinacrine sterilization

    Science.gov (United States)

    Afzal, Saira; Bukhari, Mulazim Hussain

    2014-01-01

    Objective: To describe endometrial abnormalities on transvaginal ultrasonography and histopathology in women after quinacrine sterilization. Methods: It was an analytical cross sectional study conducted during February 2012 to April 2013. The sample size calculated at 95% confidence level was 540. Sampling technique used was simple random sampling. The medical history, examination, transvaginal ultrasonography and biopsy of suspected lesion was performed in quinacrine sterilized women. Results: The calculation of statistics showed the mean age at quinacrine sterilization was 38.5 years, standard deviation 6.517, and standard error 0.461. The endometrium was regular and smooth with homogenous images in 86% (n= 466), irregular endometrium with heterogeneous images on transvaginal ultrasound in 9.4% (n =51) and endometrial growth with high level echoes in 4.2% women (n= 23). The histological findings included hyperplasia and well differentiated adenocarcinoma in two patients respectively. Conclusion: The irregular endometrium, adhesions, and growths were found after quinacrine sterilization. The risk of endometrial growth was more after 10 years duration of quinacrine sterilization. PMID:25097516

  7. Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ruijie [Department of Radiation Oncology, Peking University Third Hospital, Beijing (China); Wang, Junjie, E-mail: junjiewang47@yahoo.com [Department of Radiation Oncology, Peking University Third Hospital, Beijing (China); Xu, Feng [Department of Biomedical Engineering, Peking University Third Hospital, Beijing (China); Li, Hua [Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing (China); Zhang, Xile [Department of Radiation Oncology, Peking University Third Hospital, Beijing (China)

    2013-10-01

    To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V{sub 20} of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.

  8. Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice.

    Science.gov (United States)

    Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke

    2012-04-01

    Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

  9. Endometrial cancer; Cancer de l'endometre

    Energy Technology Data Exchange (ETDEWEB)

    Pointreau, Y.; Bernadou, G.; Barillot, I. [Service de radiotherapie, centre regional universitaire de cancerologie Henry-S.-Kaplan CHU de Tours, Hpital Bretonneau, 37 - Tours (France); Pointreau, Y. [Universite Francois-Rabelais de Tours, GICC, 37 - Tours (France); CNRS, UMR 6239 -Genetique, Immunotherapie, Chimie et Cancer-, 37 - Tours (France); CHRU de Tours, laboratoire de pharmacologie-toxicologie, 37 - Tours (France); Denis, F. [Centre Jean-Bernard, 72 - Le Mans (France); Barillot, I. [Universite Francois-Rabelais, 37 - Tours (France)

    2010-07-01

    Endometrial cancers are frequent and affect mainly postmenopausal women. They are mostly diagnosed at an early stage with an excellent prognosis. Surgery is the reference for a precise FIGO staging who guide adjuvant treatment. Tumor extension, grade, myometrium invasion and involved lymph nodes will be discriminating in therapeutic strategy. The management of stages I and II has been recently amended by ESMO, who proposed surveillance, brachytherapy, and radiation therapy followed by brachytherapy for respectively low, intermediate and high risk groups. These recommendations are controversial and must be confirmed. Locally advanced stages represent a heterogeneous population in which surgery should be proposed if it is feasible then followed by radiotherapy and/or chemotherapy. Based on an illustrated clinical case, indications, delineation, dosimetry and complications expected with radiotherapy are demonstrated. (authors)

  10. Associations between etiologic factors and mortality after endometrial cancer diagnosis: The NRG Oncology/Gynecologic Oncology Group 210 Trial

    Science.gov (United States)

    Felix, Ashley S; McMeekin, D Scott; Mutch, David; Walker, Joan L; Creasman, William T; Cohn, David E; Ali, Shamshad; Moore, Richard G; Downs, Levi S; Ioffe, Olga B; Park, Kay J; Sherman, Mark E; Brinton, Louise A

    2015-01-01

    Background Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial. Methods Prior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators. Results Median follow-up was 60 months after enrollment (range: 1 day – 118 months). Among 4,609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR=1.04, 95% CI=1.01–1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR=2.29, 95% CI=1.06–4.98, P-trend=0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR=1.05, 95% CI=1.02–1.07 per year, P-trend<0.001). Among non-endometrioid cases, endometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR=0.55, 95% CI=0.36–0.82) and carcinosarcoma cases (HR=2.01, 95% CI=1.00–4.05). Discussion Several endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis. PMID:26341710

  11. Obesity and endometrial cancer survival: a systematic review.

    Science.gov (United States)

    Arem, H; Irwin, M L

    2013-05-01

    Although it is known that obesity increases the risk of endometrial cancer and is linked to higher mortality rates in the general population, the association between obesity and mortality among endometrial cancer survivors is unclear. We performed a medline search using exploded Mesh keywords 'endometrial neoplasms/' and ('body mass index/' or 'obesity/') and ('survival analysis/' or 'mortality/' or (survivor* or survival*).mp.). We also inspected bibliographies of relevant papers to identify related publications. Our search criteria yielded 74 studies, 12 of which met inclusion criteria. Four of the included studies reported a statistically or marginally significant association between obesity and higher all cause mortality among endometrial cancer survivors after multivariate adjustment. The suggestive association between body mass index and higher all cause mortality among women with endometrial cancer was comparable to the magnitude of association reported in prospective studies of healthy women. Of the five studies that examined progression-free survival and the two studies reporting on disease-specific mortality, none reported an association with obesity. Future studies are needed to understand disease-specific mortality, the importance of obesity-onset timing and whether mechanisms of obesity-related mortality in this population of women differ from those of the general population.

  12. Obesity and endometrial cancer survival: a systematic review

    Science.gov (United States)

    Arem, H; Irwin, ML

    2013-01-01

    Although it is known that obesity increases the risk of endometrial cancer and is linked to higher mortality rates in the general population, the association between obesity and mortality among endometrial cancer survivors is unclear. We performed a medline search using exploded Mesh keywords ‘endometrial neoplasms/’ and (‘body mass index/’ or ‘obesity/’) and (‘survival analysis/’ or ‘mortality/’ or (survivor* or survival*).mp.). We also inspected bibliographies of relevant papers to identify related publications. Our search criteria yielded 74 studies, 12 of which met inclusion criteria. Four of the included studies reported a statistically or marginally significant association between obesity and higher all cause mortality among endometrial cancer survivors after multivariate adjustment. The suggestive association between body mass index and higher all cause mortality among women with endometrial cancer was comparable to the magnitude of association reported in prospective studies of healthy women. Of the five studies that examined progression-free survival and the two studies reporting on disease-specific mortality, none reported an association with obesity. Future studies are needed to understand disease-specific mortality, the importance of obesity-onset timing and whether mechanisms of obesity-related mortality in this population of women differ from those of the general population. PMID:22710929

  13. Treatment outcome after adjuvant radiotherapy following surgery for patients with stage I endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Young; Lee, Kyung Ja; Park, Kyung Ran [Dept. of Radiation Oncology, Ewha Womans University School of Medicine, Seoul (Korea, Republic of); and others

    2016-12-15

    The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0–50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.

  14. Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience.

    Science.gov (United States)

    Chen, Katherine S; Berhane, Hebist; Gill, Beant S; Olawaiye, Alexander; Sukumvanich, Paniti; Kelley, Joseph L; Boisen, Michelle M; Courtney-Brooks, Madeleine; Comerci, John T; Edwards, Robert; Berger, Jessica; Beriwal, Sushil

    2017-11-01

    Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion. Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990-2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test. 110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT±BT, with 13.6% receiving BT alone. With a median follow-up of 64.6months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy. This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  16. Global microwave endometrial ablation for menorrhagia treatment

    Science.gov (United States)

    Fallahi, Hojjatollah; Å ebek, Jan; Frattura, Eric; Schenck, Jessica; Prakash, Punit

    2017-02-01

    Thermal ablation is a dominant therapeutic option for minimally invasive treatment of menorrhagia. Compared to other energy modalities for ablation, microwaves offer the advantages of conformal energy delivery to tissue within short times. The objective of endometrial ablation is to destroy the endometrial lining of the uterine cavity, with the clinical goal of achieving reduction in bleeding. Previous efforts have demonstrated clinical use of microwaves for endometrial ablation. A considerable shortcoming of most systems is that they achieve ablation of the target by translating the applicator in a point-to-point fashion. Consequently, treatment outcome may be highly dependent on physician skill. Global endometrial ablation (GEA) not only eliminates this operator dependence and simplifies the procedure but also facilitates shorter and more reliable treatments. The objective of our study was to investigate antenna structures and microwave energy delivery parameters to achieve GEA. Another objective was to investigate a method for automatic and reliable determination of treatment end-point. A 3D-coupled FEM electromagnetic and heat transfer model with temperature and frequency dependent material properties was implemented to characterize microwave GEA. The unique triangular geometry of the uterus where lateral narrow walls extend from the cervix to the fundus forming a wide base and access afforded through an endocervical approach limit the overall diameter of the final device. We investigated microwave antenna designs in a deployed state inside the uterus. The impact of ablation duration on treatment outcome was investigated. Prototype applicators were fabricated and experimentally evaluated in ex vivo tissue to verify the simulation results and demonstrate proof-of-concept.

  17. The Role of Endocrine and Endometrial Factors in Cases of Recurrent Miscarriage: A Tertiary Center Experience

    Directory of Open Access Journals (Sweden)

    Ahmet Uysal

    2014-03-01

    Full Text Available Aim: To investigate endocrinologic and endometrial factors in cases of recurrent abortions. Material and Method: In cases of recurrent abortions, clinical and ultrasonographic features, genetic, anatomic and immunologic factors, hormonal profiles and endometrial samplings were assessed. Chromosomal abnormalities and uterine anomalies were excluded. Results: In 8 (14% of 57 cases with recurrent abortions, there were low progesterone levels. In 1 (1.75% case there was a high androgen level. In 2 (3.5% cases there was hyperprolactinemia and in another 2 (3.5% cases there were high insulin levels. In 4 (7% cases two scores of OGTT were high. In 51 cases where endometrial sampling was performed, only one (1.75% case had delayed endometrial development. Discussion: We conclude that recurrent abortions have a complex etiology related to endocrinologic and endometrial factors.

  18. Synchronous Endometrial and Ovarian Carcinoma: A Case Series

    Science.gov (United States)

    Makris, Georgios-Marios; Manousopoulou, Georgia; Battista, Marco-Johannes; Salloum, Ioannis; Chrelias, Georgios; Chrelias, Charalampos

    2017-01-01

    Synchronous ovarian and endometrial cancer (SEOC) is a rare instance but it accounts for 50–70% of all synchronous female genital tract tumors. We report three cases of women who were diagnosed with SEOC and underwent surgical staging. All cases were of the endometrioid subtype, grade 1, both in the ovarian and endometrial component. Two of them were stage Ia/Ia, and the third was stage Ib/Ib. More than 2 years after the diagnosis, all patients were alive and recurrence-free. The present report critically discusses the main characteristics, risk factors, and management of patients with SEOCs. PMID:28878658

  19. Synchronous Endometrial and Ovarian Carcinoma: A Case Series

    Directory of Open Access Journals (Sweden)

    Georgios-Marios Makris

    2017-08-01

    Full Text Available Synchronous ovarian and endometrial cancer (SEOC is a rare instance but it accounts for 50–70% of all synchronous female genital tract tumors. We report three cases of women who were diagnosed with SEOC and underwent surgical staging. All cases were of the endometrioid subtype, grade 1, both in the ovarian and endometrial component. Two of them were stage Ia/Ia, and the third was stage Ib/Ib. More than 2 years after the diagnosis, all patients were alive and recurrence-free. The present report critically discusses the main characteristics, risk factors, and management of patients with SEOCs.

  20. Aromatase inhibitor use during ovarian stimulation suppresses growth of uterine endometrial cancer in xenograft mouse model.

    Science.gov (United States)

    Kawahara, Tai; Okamoto, Naoki; Takae, Seido; Kashiwagi, Megumi; Nakajima, Mariko; Uekawa, Atsushi; Ito, Junya; Kashiwazaki, Naomi; Sugishita, Yodo; Suzuki, Nao

    2018-02-01

    Could aromatase inhibitors (AI) be used to reduce risks of uterine endometrial cancer growth or recurrence during ovarian stimulation? In a xenograft mouse model of endometrial cancer, concomitant AI administration suppressed the growth of endometrial cancer during ovarian stimulation. Recurrence and mortality rates of estrogen receptor-positive early breast cancer are reduced by long-term AI administration. Concomitant AI use for ovarian stimulation in patients with breast cancer is recommended for reducing estrogen-related potential risks. However, the efficacy of concomitant AI use for estrogen receptor-positive endometrial cancer have not been demonstrated conclusively by clinical or experimental animal studies. Forty nude mice xenografted with uterine endometrial cancer cells were allocated to four groups. Group 1: no ovarian stimulation (control). Group 2: ovarian stimulation. Group 3: AI administration + ovarian stimulation. Group 4: ovariectomy and ovarian stimulation. Tumor growth was evaluated during the 6-week treatment period. Ishikawa 3-H-12 uterine endometrial cancer cells (estrogen and progesterone receptors-positive) were transplanted into 6-week-old BALB/cSlc-nu/nu nude mice, followed by interventions 2 weeks later. Compared to ovarian stimulation alone (Group 2), significant suppressions of tumor growth were observed in other three groups (Groups 1, 3 and 4, all at P endometrial cancer tumors using one endometrial cancer cell line. Clinical endometrial cancer or hyperplasia cells can have diverse origins and AI may not be effective against other cancer cell types. Concomitant AI use may provide a chance for safer childbirth by for patients with endometrial cancer or hyperplasia. This study was supported by the Graduate Student Aid from the St. Marianna University School of Medicine. The authors declare no competing interests.

  1. Outcome of ovarian preservation during surgical treatment for endometrial cancer: A Taiwanese Gynecologic Oncology Group study

    Directory of Open Access Journals (Sweden)

    Hei-Yu Lau

    2015-10-01

    Conclusion: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.

  2. Preoperative Serum Human Epididymis Protein 4 Levels in Early Stage Endometrial Cancer: A Prospective Study.

    Science.gov (United States)

    Fanfani, Francesco; Restaino, Stefano; Cicogna, Stefania; Petrillo, Marco; Montico, Marcella; Perrone, Emanuele; Radillo, Oriano; De Leo, Rossella; Ceccarello, Matteo; Scambia, Giovanni; Ricci, Giuseppe

    2017-07-01

    The aim of the study was to evaluate the prognostic value of human epididymis protein 4 (HE4) and cancer antigen 125 markers with pathological prognostic factor to complete the preoperative clinical panel and help the treatment planning. This prospective multicenter study was conducted in 2 gynecologic oncology centers between 2012 and 2014 (Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and Catholic University of the Sacred Heart in Rome, Italy). We enrolled 153 patients diagnosed with clinical early (International Federation of Gynecology and Obstetrics stages I-II) type I endometrial cancer. Human epididymis protein 4 levels seemed to be strictly related to age (P endometrial cancer type I versus type II (P = 0.86), the lymphovascular infiltration (P = 0.12), and the cervical invasion (P = 0.6). We established a new variable, considering 3 high-risk tumor features: MI of greater than 50% and/or histological G3 and/or type II. Human epididymis protein 4 levels significantly increase in high-risk tumors (high risk HE4, 93.6 pmol/L vs low-medium risk, 65.5 pmol/L; P < 0.001). A preoperative HE4 evaluation could help stratify patients with deep invasion and/or metastatic disease and is correlated with other relevant prognostic factors to be considered to tailor an adequate surgical strategy.

  3. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women.

    Science.gov (United States)

    Wise, Michelle R; Gill, Premjit; Lensen, Sarah; Thompson, John M D; Farquhar, Cynthia M

    2016-11-01

    Clinical guidelines recommend that women with abnormal uterine bleeding with risk factors have an endometrial biopsy to exclude hyperplasia or cancer. Given the majority of endometrial cancer occurs in postmenopausal women, it has not been widely recognized that obesity is a significant risk factor for endometrial hyperplasia and cancer in young, symptomatic, premenopausal women. We sought to evaluate the effect of body mass index on risk of endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding. This was a retrospective cohort study in a single large urban secondary women's health service. Participants were 916 premenopausal women referred for abnormal uterine bleeding of any cause and had an endometrial biopsy from 2008 through 2014. The primary outcome was complex endometrial hyperplasia (with or without atypia) or endometrial cancer. Almost 5% of participants had complex endometrial hyperplasia or cancer. After adjusting for clinical and demographic factors, women with a measured body mass index ≥30 kg/m(2) were 4 times more likely to develop complex hyperplasia or cancer (95% confidence interval, 1.36-11.74). Other risk factors were nulliparity (adjusted odds ratio, 3.08; 95% confidence interval, 1.43-6.64) and anemia (adjusted odds ratio, 2.23; 95% confidence interval, 1.14-4.35). Age, diabetes, and menstrual history were not significant. Obesity is an important risk factor for complex endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding who had an endometrial biopsy in a secondary gynecology service. As over half of women with the outcome in this study were age endometrial biopsy and/or to refer secondary gynecology services. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  5. Palbociclib has antitumour effects on Pten-deficient endometrial neoplasias.

    Science.gov (United States)

    Dosil, Maria Alba; Mirantes, Cristina; Eritja, Núria; Felip, Isidre; Navaridas, Raúl; Gatius, Sònia; Santacana, Maria; Colàs, Eva; Moiola, Cristian; Schoenenberger, Joan Antoni; Encinas, Mario; Garí, Eloi; Matias-Guiu, Xavier; Dolcet, Xavier

    2017-06-01

    PTEN is one of the most frequently mutated genes in human cancers. The frequency of PTEN alterations is particularly high in endometrial carcinomas. Loss of PTEN leads to dysregulation of cell division, and promotes the accumulation of cell cycle complexes such as cyclin D1-CDK4/6, which is an important feature of the tumour phenotype. Cell cycle proteins have been presented as key targets in the treatment of the pathogenesis of cancer, and several CDK inhibitors have been developed as a strategy to generate new anticancer drugs. Palbociclib (PD-332991) specifically inhibits CDK4/6, and it has been approved for use in metastatic breast cancer in combination with letrazole. Here, we used a tamoxifen-inducible Pten knockout mouse model to assess the antitumour effects of cyclin D1 knockout and CDK4/6 inhibition by palbociclib on endometrial tumours. Interestingly, both cyclin D1 deficiency and palbociclib treatment triggered shrinkage of endometrial neoplasias. In addition, palbociclib treatment significantly increased the survival of Pten-deficient mice, and, as expected, had a general effect in reducing tumour cell proliferation. To further analyse the effects of palbociclib on endometrial carcinoma, we established subcutaneous tumours with human endometrial cancer cell lines and primary endometrial cancer xenografts, which allowed us to provide more translational and predictive data. To date, this is the first preclinical study evaluating the response to CDK4/6 inhibition in endometrial malignancies driven by PTEN deficiency, and it reveals an important role of cyclin D-CDK4/6 activity in their development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Apelin levels are higher in obese patients with endometrial cancer.

    Science.gov (United States)

    Altinkaya, S Ozlem; Nergiz, Sümeyra; Küçük, Mert; Yüksel, Hasan

    2015-02-01

    The aim of the present study was to evaluate serum concentrations of apelin, a newly discovered adipocytokine, in relation with tumor markers, metabolic profile and clinicopathologic features of patients with endometrial cancer. A total of 46 women with endometrial cancer and 44 controls were eligible for the study. Clinicopathologic features and metabolic profile as well as apelin-36 levels were evaluated in each subject. Women with endometrial cancer exhibited higher serum concentrations of apelin levels than controls (215.1 ± 59.8 pg/mL vs 177.3 ± 55.2 pg/mL, P = 0.002). Apelin levels were significantly correlated positively with body mass index, fasting insulin levels and homeostasis model assessment index (P obese (body mass index ≥ 30) and non-obese women, apelin levels remained higher in women with endometrial cancer in the obese group (P = 0.006, 243.5 ± 49.2 pg/mL vs 200.5 ± 52.7 pg/mL, respectively); whereas these levels were similar in the non-obese group (P = 0.879, 161.9 ± 37.5 pg/mL vs 159.6 ± 51.3, respectively). After adjustment for all possible confounding factors, age, apelin levels > 160 pg/mL, and diabetes mellitus were found to be associated with risk of endometrial cancer. The data of the present study suggest that higher levels of circulating apelin are associated with an increased risk of developing endometrial cancer in obese women. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  7. Obesity, diabetes, and other factors in relation to survival after endometrial cancer diagnosis.

    Science.gov (United States)

    Chia, V M; Newcomb, P A; Trentham-Dietz, A; Hampton, J M

    2007-01-01

    Endogenous and exogenous sources of estrogen and characteristics altering these hormone levels have been related to endometrial cancer risk; however, their relationship to survival following diagnosis is less clear. In a population-based study, we examined whether mortality after endometrial cancer diagnosis was affected by prediagnosis obesity, diabetes, smoking, oral contraceptive use, parity, or postmenopausal hormone (PMH) use. Eligible women, aged 40-79 years, diagnosed from 1991-1994 with incident invasive endometrial cancer and identified through the Wisconsin statewide mandatory cancer registry were invited to participate. Of 745 eligible cases, 166 women were deceased after 9.3 years of follow-up, with 43 attributable to endometrial cancer, based upon vital records linkage. Hazard rate ratios (HRR) and 95% confidence intervals were adjusted for age at diagnosis, menopausal status, stage of disease, and other exposures of interest. Obese women (body mass index [BMI] >or=30 kg/m(2)) prior to endometrial cancer diagnosis had an increased risk of both all-cause (HRR=1.6, 95% CI 1.0-2.5) and endometrial cancer (HRR=2.0, 95% CI 0.8-5.1) mortality, compared with nonoverweight women (BMIEndometrial cancer cases with diabetes also had an increased risk of all-cause mortality compared with nondiabetic women (HRR=1.7, 95% CI 1.1-2.5), although there was no association with endometrial cancer mortality. There were no associations between PMH use, oral contraceptive use, parity, or smoking and mortality from any cause. The results suggest that history of obesity and diabetes may increase risk of mortality after endometrial cancer diagnosis; modification of these characteristics may improve survival after endometrial cancer diagnosis.

  8. Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways.

    Science.gov (United States)

    Zhang, Zhenbo; Zhou, Dongmei; Lai, Yunli; Liu, Yongjuan; Tao, Xiang; Wang, Qianqian; Zhao, Guixu; Gu, Hongqin; Liao, Hong; Zhu, Yaping; Xi, Xiaowei; Feng, Youji

    2012-06-01

    Obesity is generally acknowledged as a risk factor for endometrial cancer, as accumulated adipocytes partly contribute to the increased production of estrogen which is involved in dysregulated cell growth and metastasis in early endometrial carcinogenesis. Thus we evaluated in this study expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored its role in β-estradiol (E2)-induced endometrial cancer cell proliferation and invasion. IHC staining showed that FTO overexpressed in endometrial carcinoma. Additionally, E2-induced FTO via activation of the PI3K/AKT and MPAK signal pathways contributed to enhanced proliferation and invasion. Therefore, this study provides a new insight on the mechanisms of E2-induced proliferation and invasion and the link between obesity and endometrial cancer, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Obesity-associated endometrial and cervical cancers.

    Science.gov (United States)

    Gu, Wenyi; Chen, Chen; Zhao, Kong-Nan

    2013-01-01

    Epidemiological studies have indicated that obesity (body mass index-BMI>30) and overweight (BMI>25) directly associated with risk of many cancers. The association of obesity with cancer risks may be explained by the alterations in the metabolism of endogenous hormones, production of specific proteins and cytokines, adipose related inflammatory reactions, and genetic factors. This review aims to illustrate the link between obesity and occurrence and prognosis of endometrial and cervical cancers. Convincing scientific evidence shows that nutrition and lifestyle factors initiate the development of obesity with excessive adipose tissues, which trigger production of hormones, cytokines and other factors to promote growth of cancer cells. Obese women with either endometrial or cervical cancer, especially in postmenopausal period, have shown a significantly higher mortality. This is mainly due to that the obese women are more vulnerable in cancer occurrence and they are more likely to miss routine cancer screening, putting them at a greater risk for delayed diagnosis of these cancers and deteriorate prognosis. Thus, healthcare providers should pay particular attention to this more vulnerable group of women.

  10. [Impaired endometrial receptivity in primary infertility in women with undifferentiated connective tissue dysplasia and hereditary thrombophilia].

    Science.gov (United States)

    Zanozin, A S; Demura, T A; Kolosovsky, D Yu; Faizullina, N M; Kogan, E A

    The concurrence of undifferentiated connective tissue dysplasia (uCTD) and hereditary thrombophilia (HT) often accompanies female infertility, in the pathogenesis of which impaired endometrial receptivity plays an important role. to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT. The pipelle endometrial biopsy specimens taken in the implantation window were examined in 81 patients, including 13 women with a clinical diagnosis of uCTD, 40 with HT, 19 with uCTD concurrent with HT, and in a control group of 9 heathy surrogate mothers. Morphological, immunohistochemical, and morphometric examinations were done to study the paraffin-embedded endometrial biopsy sections stained with hematoxylin and eosin, pikrofuksin by van Gieson, and with toluidine blue. Immunohistochemical tests were carried out using primary antibodies against ER, PgR, LIF, PAI-1, VEGF, Collagen I, Collagen III, fibronectin, laminin, MMP-2, and MMP-9. The uCTD, HT, and uCTD + HT groups were found to have signs of decreased endometrial receptivity as dramatically lower counts of mature pinopodes, slower endometrial maturation, reduced expression of the receptivity marker LIF, and deviations of the stromal progesterone-estrogen index from the normal value. Sclerotic foci with type III collagen accumulation were detected in the endometrial stroma. uCTD and HT and especially their concurrence are commonly a concomitant disease and risk factors for infertility in women due to impaired endometrial receptivity. In uCTD, connective tissue remodeling processes are substantially retarded, which ultimately leads to increased processes of endometrial stromal sclerosis, reduced endometrial receptivity, and infertility. The most pronounced morphological and immunophenotypical changes have been ascertained to develop in the uCTD + NT group. The findings may be used to predict and devise new infertility treatments in patients

  11. Body mass index and the quality of life of endometrial cancer survivors-A systematic review and meta-analysis

    NARCIS (Netherlands)

    Smits, A.; Lopes, A.; Bekkers, R.L.; Galaal, K.

    2015-01-01

    BACKGROUND: Obesity is a risk factor for developing endometrial cancer and known to negatively affect outcomes and survival. However, the association between obesity and quality of life of endometrial cancer survivors (ECS) remains unclear. OBJECTIVES: To assess the association between body mass

  12. The impact on survival of two different staging strategies in apparent early stage endometrial cancer comparing sentinel lymph nodes mapping algorithm and selective lymphadenectomy: An Italian retrospective analysis of two reference centers.

    Science.gov (United States)

    Buda, Alessandro; Di Martino, Giampaolo; Restaino, Stefano; De Ponti, Elena; Monterossi, Giorgia; Giuliani, Daniela; Ercoli, Alfredo; Dell'Orto, Federica; Dinoi, Giorgia; Grassi, Tommaso; Scambia, Giovanni; Fanfani, Francesco

    2017-12-01

    The role of lymphadenectomy in endometrial cancer is still uncertain. We aimed to evaluate the survival outcomes of two different strategies in apparent uterine confined disease by comparing sentinel lymph node (SLN) mapping and selective lymphadenectomy (LD). We retrospectively reviewed women with preoperative stage I endometrial cancer underwent surgical staging with either SLN mapping, or LD in two Italian centers. Eight hundred and two women underwent surgical staging for preoperative stage I endometrial cancer were revised (145 Monza; 657 Rome). All patients underwent peritoneal washing, simple hysterectomy with bilateral salpingo-oophorectomy and nodal staging including SLN mapping, or LD. Overall 8229 lymph nodes were removed (1595 in Monza, 6634 in Rome). Pelvic lymphadenectomy was performed in 33.1% and 52.4% in Monza and Rome, respectively (pendometrial cancer patients. The clinical impact and management of low volume metastasis in high-risk patients should be further clarify. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Prospective study of combined colon and endometrial cancer screening in women with lynch syndrome: a patient-centered approach.

    Science.gov (United States)

    Huang, Marilyn; Sun, Charlotte; Boyd-Rogers, Stephanie; Burzawa, Jennifer; Milbourne, Andrea; Keeler, Elizabeth; Yzquierdo, Rebecca; Lynch, Patrick; Peterson, Susan K; Lu, Karen

    2011-01-01

    Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability. From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores. Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P Lynch syndrome screening recommendations.

  14. CXCL12/CXCR4 axis induces proliferation and invasion in human endometrial cancer.

    Science.gov (United States)

    Liu, Pingping; Long, Ping; Huang, Yu; Sun, Fengyi; Wang, Zhenyan

    2016-01-01

    Since that we have previously found CXCL12/CXCR4, an important biological axis is highly transcribed in several cancer cells. We aim to investigate whether CXCL12/CXCR4 axis regulates critical processes in neoplastic transformation that affects endometrial cancer cell biology. The expression levels of CXCR4 were analyzed in human normal endometrial tissue, simple hyperplasia, atypical hyperplasia and endometrial cancer cells by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Serum CXCL12 was measured by Enzyme-Linked Immunosorbent Assay (ELISA) in Ishikawa endometrial cancer cell line. To study the biological function of CXCL12/CXCR4 in endometrial cancer, short interfering RNA silencing of CXCR4 was established to analyze the roles of CXCL12/CXCR4 in proliferation, migration, invasion and apoptosis of Ishikawa cells in vitro. The expression level of CXCR4 in endometrial cancer tissue was higher as compared to atypical hyperplasia, simple hyperplasia and normal cycling endometrium cells. Ishikawa cells secreted CXCL12 spontaneously and continuously for 96 hrs in culture. The proliferation, migration and invasion of Ishikawa cells was significantly induced, and the apoptosis was significantly reduced by CXCL12 in combination with CXCR4. Moreover, CXCR4 silencing could significantly antagonize all these functions. CXCL12/CXCR4 axis plays an important role in the proliferation, invasion and metastasis of endometrial cancer, indicating that CXCR4 could be the target for the treatment of endometrial cancer.

  15. Utility of the Ultrasound Evaluation of Intraperitoneal Fat in Correlation with Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Răzvan CIORTEA

    2011-03-01

    Full Text Available Introduction: In the context of endometrial cancer, visceral obesity as a risk factor is associated with a chronic inflammatory process, confirmed by the increase in inflammatory marker levels. Material and Method: The study is a case-control analysis including 2 groups of patients: group I – 50 patients diagnosed with endometrial cancer, group II – 70 patients without gynecological pathology or inflammatory disorders (control group. The diagnosis of endometrial cancer was made following histopathological examination that evaluated the tissue material obtained following endometrial biopsy. After clinical examination and anthropometric measurements, these patients underwent ultrasound and computer tomography examination by which intraperitoneal fat was determined. All parameters were included in the study database. Results: A significant correlation coefficient was also found between visceral fat evaluated by CT and visceral fat assessed by US (r =0.96, p<0.0001. In the case of the control group, the mean visceral fat area was 159.14±42.5 cm², while in the group of patients with endometrial cancer, the mean visceral fat area was 251.37±59.78 cm². Thus, there is a statistically significant difference in intraperitoneal fat between the two groups (p<0.0001. Conclusions: A visceral fat area larger than 250 cm² is a risk factor for endometrial cancer. The measurement of visceral fat by US can be a screening method for endometrial cancer in obese patients.

  16. Association of abnormal glucose metabolism and insulin resistance in patients with atypical and typical endometrial cancer.

    Science.gov (United States)

    Lai, Yongjing; Sun, Chuanying

    2018-02-01

    This study aimed to detect glucose metabolism indicators and insulin resistance index in patients with endometrial cancer, and to explore the clinical significance and correlation between them. A total of 65 patients with endometrial cancer (52 of typical endometrial and 13 cases of atypical endometrial cancer patients, 27 with diabetes mellitus, and 38 cases without diabetes mellitus) were selected at the People's Hospital of Rizhao from June, 2010 to June, 2016 to serve as the observation group. During the same period, 62 patients with endometrial benign lesions (24 with diabetes mellitus and 38 cases without diabetes mellitus) were selected as the control group. General information including height, body weight, body mass index (BMI), abdominal, waist and hip circumference, and waist-to-hip ratio (WHR) was compared between the two groups. Fasting blood glucose, glycosylated hemoglobin, fasting insulin level (FINS), insulin resistance index (HOMA-IR), follicle estrogen (FSH), luteinizing hormone and estradiol (estrogen) were detected and compared between the two groups. Multivariate logistic regression was used to analyze the risk factors for endometrial cancer. The results showed that there were no significant differences in the height and hip circumference among the typical, atypical and control groups. By contrast, weight, BMI, waist circumference, abdominal circumference and the WHR of the typical group were significantly higher than those of the atypical and control groups (P0.05). Levels of the FINS and HOMA-IR typical group were significantly higher than those in the atypical and control groups, and the incidence of hyperinsulinemia and insulin resistance was significantly higher in the observation than in the control group (Pendometrial cancer patients with different pathological features (P>0.05). HOMA-IR (OR=1.240), estrogen (OR=1.192) and FSH (OR=1.002) are risk factors for endometrial cancer. The results suggest that hyperinsulinemia and insulin

  17. Early Detection of High Risk Pregnancy

    OpenAIRE

    Kurniawan, Arif; Sistiarani, Colti; Hariyadi, Bambang

    2017-01-01

    There are 30.939 pregnant women in Banyumas, with 6.206 cases referred due to high-risk pregnancies. Petahunan village in Pekuncen has the the highest incidence of high-risk pregnancies compared with other villages. The purpose of this study is to describe the implementation of early detection of high-risk pregnancies in Petahunan village, Pekuncen. This study used qualitative research methods with case study approach. Research instruments used in-depth interviews and focus group disscussion ...

  18. [Socioeconomic factors in high risk pregnancy].

    Science.gov (United States)

    Armas Domínguez, J; Shor Pinsker, V; Mac Gregor, C; Karchmer, S

    1977-05-01

    The study of high risk during pregnancy was undertaken to show the most viable ways for solving those problems affecting maternal-fetal morbidity and mortality. The authors are hopeful that in the future, the 2 branches of medicine, perinatology and obstetrics, will no longer differentiate between high risk for mother and fetus or neonate but will direct attention to what is high risk for 1 society in particular. These professionals will undertake an interdisciplinary approach of the problem to benefit society. (author's)

  19. Endometrial cancer with cervical extension mimicking dual concordant endometrial and cervical malignancy by F18 FDG PET and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Seok Nam [Kwandong Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    A 35 year old woman with endometrial cancer and cervical extension underwent F18 FDG PET CT and MRI studies after resection of a cervical mass presumed to be cervical myoma. The patient underwent cervical myomectomy and the histopathologic report revealed poorly differentiated invasive carcinoma. Cervical cancer was ruled out because the patient had no history of sexual intercourse and was negative for human papilloma virus infection. The patient underwent radical hysterectomy, bilateral salpingo oophorectomy, pelvic and para aortic lymph node dissection, and multiple biopsies. F18 FDG PET CT showed intense FDG uptake along the cervix wall. T2 weighted MRI also revealed a mass lesion with high SI involving the anterior and posterior lips of the uterine cervix. Another area of focal increased uptake above the endometrial lesion in the left pelvic cavity was observed on PET CT and MRI, possibly due to a functioning ovary. PET CT and MRI were interpreted as showing a dual concordant malignant lesion due to separated FDG uptakes and high SI without any connection between the cervical and endometrial lesions. F18 FDG PET CT showed intense FDG uptake along the endometrium. Given the patient's history and the fact that she was not menstruating at the time of imaging, this intense uptake was interpreted as another pathologic lesion, suggesting dual primary lesions. A suspected heterogeneous mass lesion along the endometrium suggesting concordant endometrial cancer was found on MRI. Endometrial cancer with cervical extension is sometimes difficult to differentiate from primary cervical cancer. The final histopathologic report showed poorly differentiated endometrial adenocarcinoma with cervical extension, although the FDG PET CT and MRI findings were suggestive of concordant cervical and endometrial cancer. Although histopathologic confirmation is necessary for final diagnosis, MRI and FDG PET CT studies may aid in the differential diagnosis. A metastatic cervical mass

  20. 21 CFR 884.1060 - Endometrial aspirator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 884.1060 Endometrial aspirator. (a) Identification. An endometrial aspirator is a device designed to...

  1. Robotic surgery in supermorbidly obese patients with endometrial cancer.

    Science.gov (United States)

    Stephan, Jean-Marie; Goodheart, Michael J; McDonald, Megan; Hansen, Jean; Reyes, Henry D; Button, Anna; Bender, David

    2015-07-01

    Morbid obesity is a known risk factor for the development of endometrial cancer. Several studies have demonstrated the overall feasibility of robotic-assisted surgical staging for endometrial cancer as well as the benefits of robotics compared with laparotomy. However, there have been few reports that have evaluated robotic surgery for endometrial cancer in the supermorbidly obese population (body mass index [BMI], ≥50 kg/m(2)). We sought to evaluate safety, feasibility, and outcomes for supermorbidly obese patients who undergo robotic surgery for endometrial cancer, compared with patients with lower body mass indices. We performed a retrospective chart review of 168 patients with suspected early-stage endometrial adenocarcinoma who underwent robotic surgery for the management of their disease. Analysis of variance and univariate logistic regression were used to compare patient characteristics and surgical variables across all body weights. Cox proportional hazard regression was used to determine the impact of body weight on recurrence-free and overall survival. The mean BMI of our cohort was 40.9 kg/m(2). Median follow up was 31 months. Fifty-six patients, 30% of which had grade 2 or 3 tumors, were supermorbidly obese with a BMI of ≥50 kg/m(2) (mean, 56.3 kg/m(2)). A comparison between the supermorbidly obese and lower-weight patients demonstrated no differences in terms of length of hospital stay, blood loss, complication rates, numbers of pelvic and paraaortic lymph nodes retrieved, or recurrence and survival. There was a correlation between BMI and conversion to an open procedure, in which the odds of conversion increased with increasing BMI (P = .02). Offering robotic surgery to supermorbidly obese patients with endometrial cancer is a safe and feasible surgical management option. When compared with patients with a lower BMI, the supermorbidly obese patient had a similar outcome, length of hospital stay, blood loss, complications, and numbers of lymph

  2. How much is another randomized trial of lymph node dissection in endometrial cancer worth? A value of information analysis.

    Science.gov (United States)

    Havrilesky, Laura J; Chino, Junzo P; Myers, Evan R

    2013-10-01

    This study aimed to assess the value of a randomized controlled trial (RCT) of lymph node dissection (LND) at the time of hysterectomy for high-risk subsets of women with endometrial cancer. A modified Markov decision model compared routine LND to no LND for women with grade 3 or grades 2-3 endometrial cancer. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity and value of information (VOI) analyses. Survival without LND was modeled from Surveillance, Epidemiology and End Results program data. A hazard ratio (HR) describing survival in the high-risk group undergoing LND (estimate 0.9, 95% CI 0.6-1.1), adverse event rates, probability and type of adjuvant therapy were modeled from published RCTs. Costs were obtained from national reimbursement data. VOI estimated the value of reducing uncertainty regarding the survival benefit of LND. For grade 3, LND had an incremental cost-effectiveness ratio of $40,183/quality-adjusted life year (QALY) compared to no LND. Acceptability curves revealed considerable uncertainty, with an expected value of perfect information of $4,195 per patient at societal willingness to pay of $50,000/QALY. The estimated value of partial perfect information regarding the HR was $3,702 per patient. Assuming 8,000 individuals annually with grade 3 endometrial cancer in the US, the upper limit of VOI for the HR was $29.6 million annually. For grades 2 and 3 combined, analysis revealed a much lower likelihood of finding LND cost-effective. A clinical trial defining the survival effect of LND in women with grade 3 endometrial cancer is a worthwhile use of resources. © 2013.

  3. Good practice with endometrial ablation.

    Science.gov (United States)

    Garry, R

    1995-07-01

    To provide clear guidelines for the safe and effective performance of endometrial ablation. Representatives of American, Australian, British, and Canadian hysteroscopists were brought together to produce a consensus document of good practice in endometrial ablation. The guidelines were produced after researching the literature, combining the extensive experience of the group, and debating the relevant issues. Endometrial ablation is a new procedure. Correct patient selection is essential in producing good results. Patients must be counseled carefully about the advantages, disadvantages, and potential complications of this approach to the management of menstrual disorders. The main indication for endometrial ablation is heavy menstrual loss in the absence of organic disease. Excessive uterine size, the presence of active pelvic infection, and evidence of malignant and premalignant endometrium are absolute contraindications. Ablation can be produced by electrosurgical resection, rollerball or rollerbarrel ablation and Nd-YAG laser ablation. Severe complications can occur, and techniques should be adopted to avoid uterine perforation, hemorrhage, and excessive fluid absorption. In skilled hands, endometrial ablation can be a safe and effective treatment for menorrhagia.

  4. [Overweight, obesity, diabetes, and hypertension in endometrial cancer].

    Science.gov (United States)

    Sanz-Chávez, Tania L N; Vilar-Compte, Diana; de Nicola-Delfín, Luigina; Meneses-García, Abelardo

    2013-01-01

    in postmenopausal women, the excess of fat has been associated with an increased risk of endometrial cancer. The aim of the study was to determine the prevalence of overweight, obesity, diabetes and hypertension in patients with endometrial cancer. we collected demographic, clinical, laboratory and histopathological information from the electronic records of patients diagnosed with endometrial cancer in the period from January 2009 to July 2011. Subsequently descriptive analysis of the information was done. a total of 274 records. The average age of patients was 54 years. The 50.4 % were postmenopausal. At the time of diagnosis, 112 cases (48.6 %) were in clinical stage I. Of all patients, 104 (37.9 %) had diabetes mellitus, 122 (44.5 %) hypertension, 194 (72.6 %) were overweight or obese, and 24 cases were registered with the metabolic syndrome. in regards to this diagnosis the results show a higher incidence of overweight and obesity compared with other countries. It is necessary to conduct further studies to assess the relationship of excess fat as a risk factor for endometrial cancer.

  5. Low risk and high risk human papillomaviruses (HPVs) and cervical ...

    African Journals Online (AJOL)

    Low risk and high risk human papillomaviruses (HPVs) and cervical cancer in Zimbabwe: epidemiological evidence. M Chirara, G A Stanczuk, S A Tswana, L Nystrom, S Bergstrom, S R Moyo, M J Nzara. Abstract. No Abstract. Central African Journal of Medicine Vol. 47 (2) 2001: pp. 32-34.

  6. Utility of conventional and diffusion-weighted MRI features in distinguishing benign from malignant endometrial lesions

    Energy Technology Data Exchange (ETDEWEB)

    Kierans, Andrea S., E-mail: Andrea.Kierans@nyumc.org; Bennett, Genevieve L., E-mail: Genevieve.Bennett@nyumc.org; Haghighi, Mohammad, E-mail: haghighi549@gmail.com; Rosenkrantz, Andrew B., E-mail: Andrew.Rosenkrantz@nyumc.org

    2014-04-15

    Purpose: To evaluate the utility of conventional MRI and diffusion-weighted imaging (DWI) in differentiating benign from malignant endometrial lesions. Methods: 52 patients with an abnormal endometrium on MRI and subsequent pathologic evaluation (35 benign, 17 malignant) were included. Two radiologists (R1, R2) independently evaluated endometrial abnormalities for characteristics on conventional MRI and DWI. Findings were assessed using unpaired t-tests, Fisher's exact test, and multi-variate logistic regression. Results: Findings with significantly higher frequency in malignant abnormalities were: presence of irregularly marginated endometrial lesion (R1: 71% vs. 34%, R2: 94% vs. 26%), irregular endo-myometrial interface on T2WI (R1: 77% vs. 26%, R2: 94% vs. 29%), irregular endo-myometrial interface on post-contrast T1WI (R1: 82% vs. 23%, R2: 88% vs. 20%), increased signal on high b-value DWI (R1: 82% vs. 20%, R2: 94% vs. 20%), decreased ADC (R1: 88 vs. 40%, R2: 94% vs. 20%) (all p < 0.001, both readers). Endometrial thickness, presence of any focal endometrial lesion regardless of contour, diameter of endometrial lesion, endometrial heterogeneity on T2WI, decreased T2 signal, and increased endometrial enhancement, failed to show significant differences between groups (all p ≥ 0.159, both readers). At multivariate analysis, for R1, irregular endo-myometrial interface on post-contrast T1WI and increased DWI signal were significant independent predictors of malignancy (AUC = 0.89); for R2, only increased DWI signal was a significant independent predictor of malignancy (AUC = 0.87). Conclusion: Abnormal signal on DWI and irregularity of either the endo-myometrial interface or focal endometrial lesion were the most helpful MRI features in differentiating benign from malignant endometrial abnormalities.

  7. Obesity and Endometrial Cancer: A Lack of Knowledge but Opportunity for Intervention.

    Science.gov (United States)

    Haggerty, Ashley F; Sarwer, David B; Schmitz, Kathryn H; Ko, Emily M; Allison, Kelly C; Chu, Christina S

    2017-10-01

    The causal link between obesity and endometrial cancer is well established; however obese women's knowledge of this relationship is unknown. Our objective was to explore patients' understanding of this relationship and assess the acceptability of a technology-based weight loss intervention. Obese women with Type I endometrial cancer/hyperplasia were surveyed about their assessment of their body mass, knowledge of the relationship of obesity and endometrial cancer, and eating and activity habits. Interest in participation in an intervention also was assessed. Eighty-one women with early stage (71.6% stage I) and grade (41.7% grade 1) disease completed the survey. The median BMI was 35.4 kg/m(2) (IQR 32.2-43.5 kg/m(2)) and the average age was 59.3 (SD 11.1) yr. 76.25% of women were unable to categorize their BMI correctly and 86.9% of those incorrectly underestimated their BMI category. One-third (35.9%) were unaware of any association between obesity and endometrial cancer and 33.3% responded that obesity decreased or did not significantly increase the risk of endometrial cancer. 59% expressed interest in a weight loss intervention. Endometrial cancer survivors with obesity underestimated their obesity and lacked knowledge regarding the link between obesity and endometrial cancer. However, the majority expressed interest in electronically delivered weight loss interventions.

  8. The Results and Prognostic Factors of Postoperative Radiation Therapy in the Early Stages of Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ja [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2008-09-15

    To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial

  9. HMGB1 is negatively correlated with the development of endometrial carcinoma and prevents cancer cell invasion and metastasis by inhibiting the process of epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Luan XR

    2017-03-01

    Full Text Available Xiaorong Luan,1,2 Chunjing Ma,2 Ping Wang,2 Fenglan Lou1 1Nursing College, Shandong University, 2Qilu Hospital of Shandong University, Jinan, People’s Republic of China Abstract: High-mobility group box protein 1 (HMGB1, a nuclear protein that plays a significant role in DNA architecture and transcription, was correlated with the progression of some types of cancer. However, the role of HMGB1 in endometrial cancer cell invasion and metastasis remains unexplored. HMGB1 expression was initially assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR in normal endometrial tissue and endometrial carcinoma tissue. High expressions of HMGB1 protein were detected in normal endometrial tissues; however, in endometrial cancer tissues, the expressions of HMGB1 were found to be very weak. Furthermore, HMGB1 expressions were negatively correlated with advanced stage and lymph node metastasis in endometrial cancer. Then by RT-qPCR, Western blot and immunocytochemistry, HMGB1 was also detected in primary cultured endometrial cells and four kinds of endometrial cancer cell lines (Ishikawa, HEC-1A, HEC-1B and KLE. We found that the expression of HMGB1 was much higher in normal endometrial cells than in endometrial cancer cells, and reduced expression levels of HMGB1 were observed especially in the highly metastatic cell lines. Using lentivirus transfection, HMGB1 small hairpin RNA was constructed, and this infected the lowly invasive endometrial cancer cell lines, Ishikawa and HEC-1B. HMGB1 knockdown significantly enhanced the proliferation, invasion and metastasis of endometrial cancer cells and induced the process of epithelial-to-mesenchymal transition. These results can contribute to the development of a new potential therapeutic target for endometrial cancer. Keywords: HMGB1, endometrial cancer, invasion, metastasis, epithelial-to-mesenchymal transition

  10. Role of emmprin in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Nakamura Keiichiro

    2012-05-01

    Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. Results The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p p p  Conclusions The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.

  11. Value of endometrial thickness assessed by transvaginal ultrasound for the prediction of endometrial cancer in patients with postmenopausal bleeding.

    Science.gov (United States)

    Schramm, Amelie; Ebner, Florian; Bauer, Emanuel; Janni, Wolfgang; Friebe-Hoffmann, Ulrike; Pellegrino, Miriam; De Gregorio, Nikolaus; Friedl, Thomas W P

    2017-08-01

    Histological confirmation of endometrial cancer by dilatation/curettage (D/C) in women with postmenopausal bleeding (PMB) can be challenging due to anesthesiological and/or surgical risks. Thus, less invasive methods for diagnostics are required to identify patients with minimal risk for endometrial cancer (EC) to avoid unnecessary surgical intervention. The objective of this single-center cohort study was to assess the diagnostic validity of transvaginal ultrasound (TVUS) measurements of endometrial thickness (ET) in patients with PMB for the detection of EC. A retrospective analysis of data from patients presenting between January 2005 and August 2014 at the Department of Obstetrics and Gynecology, University Hospital Ulm, Germany, with PMB and subsequent D/C was performed. Complete data with TVUS documentation of ET and histological results of tissue samples were available from 254 patients. In addition, data on age, body mass index (BMI), ASA-score, diabetes, hypertension, and hematological laboratory values (for a smaller subsample) were recorded. To identify independent risk factors, a multivariate logistic regression with endometrial cancer as binary response variable (yes/no) was performed. Diagnostic efficacy data for different ET cutoff points (≤1 to ≤26 mm) were obtained by a receiver operator characteristic (ROC) curve analysis. The multivariate logistic regression revealed a significant independent predictive value for age and ET. However, none of the analyzed ET cutoff points showed optimal diagnostic validity, as all cutoff points with sensitivity rates above 90% (≤1 to ≤5 mm) had false positive rates of 70% and higher. There is no ET cutoff point that provides good diagnostic accuracy and/or reliably excludes the presence of endometrial cancer in patients with PMB. Thus, our data analysis supports the actual German approach of histological evaluation of any PMB to confirm or exclude EC.

  12. High risk of permafrost thaw

    Science.gov (United States)

    E.A.G. Schuur; B.W. Abbott; W.B. Bowden; V. Brovkin; P. Camill; J.P. Canadell; F.S. Chapin; T.R. Christensen; J.P. Chanton; P. Ciais; P.M. Crill; B.T. Crosby; C.I. Czimczik; G. Grosse; D.J. Hayes; G. Hugelius; J.D. Jastrow; T. Kleinen; C.D. Koven; G. Krinner; P. Kuhry; D.M. Lawrence; S.M. Natali; C.L. Ping; A. Rinke; W.J. Riley; V.E. Romanovsky; A.B.K. Sannel; C. Schadel; K. Schaefer; Z.M. Subin; C. Tarnocai; M. Turetsky; K. M. Walter-Anthony; C.J. Wilson; S.A. Zimov

    2011-01-01

    Arctic temperatures are rising fast, and permafrost is thawing. Carbon released into the atmosphere from permafrost soils will accelerate climate change, but the magnitude of this effect remains highly uncertain. Our collective estimate is that carbon will be released more quickly than models suggest, and at levels that are cause for serious concern. We calculate that...

  13. Endometrial carcinoma; Endometriumkarzinom

    Energy Technology Data Exchange (ETDEWEB)

    Engelhard, K. [Krankenhaus Martha-Maria, Nuernberg (Germany)

    2011-07-15

    Magnetic resonance imaging (MRI) is the method of choice in staging endometrial cancer. Using MRI early tumor invasion (stage IA) can be differentiated from a deep tumor growth (stage IB) of the myometrium with reported sensitivities of 85-95%.Tumor invasion of the uterine cervix can be depicted with a sensitivity of 80% and specificity of 96%. In demonstrating lymph node metastases MRI shows a sensitivity of 50%, a specificity of 95% and and accuracy of 90%. These diagnostic criteria are decisive for the choice of therapy procedures. So a simple hysterectomy will be performed in early stage IA disease while an extended surgical procedure with pelvic lymphadenectomy and radiotherapy will be considered in advanced stages IB and II disease. Vaginal ultrasound shows lower values in tumor staging with accuracies of 73-95%. Staging accuracies of computed tomography also show lower results with 61-76%. For planning radiotherapy and detection of cancer recurrence MRI is the most valuable tool. (orig.) [German] Fuer die Stadieneinteilung des Endometriumkarzinoms ist die Magnetresonanztomographie Methode der Wahl. Die Sensitivitaeten zur Differenzierung einer oberflaechlichen (Stadium IA) von einer tiefen myometrialen Invasion des Tumors (Stadium IB) liegen bei 85-95%, bei Spezifitaeten von 80-85%. Eine Infiltration der Zervix (Stadium II) kann mit Sensitivitaeten von 80% und Spezifitaeten von 96% nachgewiesen werden. Bei der Detektion von Lymphknotenmetastasen liegen die Sensitivitaeten der MRT bei 50%, bei Spezifitaeten von 95% und Treffsicherheiten von 90%. Die genannten diagnostischen Kriterien bestimmen das therapeutische Vorgehen. Werden fruehe Stadien mit einfacher Hysterektomie behandelt, erfordern die Stadien IB und II kombinierte erweiterte chirurgische Techniken und eine Radiotherapie. Die Treffsicherheiten des vaginalen Ultraschalls (73-93%) und der Computertomographie (61-76%) fuer die Stadieneinteilung des Tumors liegen deutlich niedriger als die Werte fuer

  14. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration

    Directory of Open Access Journals (Sweden)

    Delphine Haouzi

    2014-01-01

    Full Text Available The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

  15. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  16. Predictors of limph node metastasis in endometrial cancer.

    Science.gov (United States)

    Ignat, Florin Laurentiu; Irimie, Alexandru; Costin, Nicolae; Achimas-Cadariu, Patriciu; Lisencu, Ioan Cosmin

    2013-01-01

    Endometrial cancer is the most common gynecologic malignancy in developed countries. The adequate surgical staging proposed by FIGO (International Federation for Gynaecology and Obstetrics) advocates lymphadenectomy; however, it does not establish the indications, the type and the extent of lymphadenectomy, thus generating multiple controversies. Retrospective, analytical study of patients treated surgically for endometrial adenocarcinoma in the Oncological Institute "Prof. Dr. Ion Chiricuţă" Cluj-Napoca (IOCN) between January 2008 and December 2012 - 709 cases eligible for the study. 206 pelvic and/or paraaortic lymphadenectomies were performed, the average number of excised lymph nodes being 15.6. Overall in 4.4% of patients the lymph nodes were affected by metastases. The presence of each risk factor analysed was statistically significantly associated with lymph node metastasis (p<0.05). Age above 55 years was statistically significantly associated (p<0.05) with the presence of negative prognostic factors in the study. The analysed histopathological and clinical prognostic factors were statistically significantly associated with lymphatic dissemination in endometrial cancer. We recommend treating endometrial cancer in tertiary centres by surgeons or gynaecologists-oncologists with experience in extensive peritoneal and retroperitoneal surgery.

  17. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  18. Endometrial cytopathology. An image analysis approach using the Ki-67 biomarker.

    Science.gov (United States)

    Apostolou, G; Apostolou, N; Moulos, P; Chatzipantelis, P

    2017-10-01

    To investigate the different identity and biological behaviour of endometrial benign epithelial and endometrial adenocarcinoma cell categories. For this study, the imprint smears from three groups, 10 cases of disordered proliferative/benign hyperplastic endometrium, 21 cases of low-grade and eight cases of high-grade endometrial adenocarcinoma, were examined using image analysis and the Ki-67 biomarker. The plastic stem cell model was also applied. Among the examined groups, the nuclear area major axis ranged statistically different in the digitally measured Ki-67 positive endometrial epithelial and adenocarcinoma cells (Pendometrial adenocarcinomas (Pendometrial lesions, and a relatively stable pathway was noticed in low- and high-grade endometrial adenocarcinomas. The different range of the nuclear area major axis among cycling endometrial epithelial and adenocarcinoma cells may correlate with their specific identity and biological behaviour. The different values of the cycling nuclear area major dimension may also be connected with the biological behaviour of the three examined groups. Moreover, the endometrial epithelial cells may follow a Ki-67 increase pathway, instead of the relatively stable pathway which the rapidly proliferating adenocarcinoma cells may use. Finally, the studied cell categories may exhibit different biology, because their stem cells may reside in different states of stemness. © 2017 John Wiley & Sons Ltd.

  19. Obesity and prognosis in endometrial cancer.

    Science.gov (United States)

    Anderson, B; Connor, J P; Andrews, J I; Davis, C S; Buller, R E; Sorosky, J I; Benda, J A

    1996-04-01

    We tested the null hypothesis that morbid obesity as measured by the Quetelet index has no influence on survival in endometrial cancer. A retrospective study of 492 women with endometrial carcinoma was performed. Age, height, weight, Quetelet index, stage, cell type, grade, node status, peritoneal cytologic findings, and depth of myometrial invasion were analyzed for influence on survival. Mean Quetelet index was 34 (range 16 to 89). Quetelet index was 40 in 22%. Five percent of those with a Quetelet index > 40 had positive nodes, but 64% of patients with a Quetelet index > 40 did not have lymph node sampling done. Lack of sampling of lymph nodes in the entire group had no adverse effect on survival. In a proportional hazards regression model for time from diagnosis to death from disease, grade, node status, myometrial invasion, and stage had highly significant effects. When Quetelet index was analyzed as a continuous variable, as Quetelet index increased, time to recurrence was significantly increased (p = 0.0136), and significance was approached for survival (p = 0.0645). Quetelet index was strongly related to grade (p = 0.013), depth of myometrial invasion (p = 0.031), negative cytologic findings (p = 0.004), and stage (p = 0.011) with obese patients having better differentiated, less invasive tumors of lower stage with negative washings. Morbid obesity positively affects survival in endometrial carcinoma. This effect is accounted for by the association of obesity with less aggressive disease. Morbid obesity is not associated with increased death from other causes. Lack of sampling of negative lymph nodes does not adversely affect survival.

  20. Endometrial changes during ulipristal acetate use: A systematic review.

    Science.gov (United States)

    De Milliano, Inge; Van Hattum, Dominique; Ket, Johannes C F; Huirne, Judith A F; Hehenkamp, Wouter J K

    2017-07-01

    Ulipristal acetate is increasingly used for several clinical indications, like emergency contraception and pre-treatment of uterine fibroids. It has mixed progesterone agonist and antagonist effects in the myometrium and endometrium. Due to its progesterone antagonistic effect, an unopposed estrogen effect could occur which could cause (pre-)malignant lesions in the endometrium. Several studies have been performed to evaluate this possible increased risk for endometrial malignancies when using ulipristal acetate. The specific spectrum of morphological changes due to ulipristal acetate, named progesterone receptor modulator associated endometrial changes (PAEC), occurs to be reversible after discontinuing ulipristal acetate. In this systematic review we provide a detailed overview of the literature on histopathological endometrial changes and imaging characteristics of the endometrium in ulipristal acetate users. We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed in accordance with the prisma guidelines. All studies published as full papers in peer reviewed journals using ulipristal acetate reporting on endometrial changes were included, independent of clinical indication, dosage taken and duration of therapy. No language restrictions were applied. Ten studies with a total of 1450 participants were included. Seven were randomized clinical trials and three prospective cohort studies. A quality assessment of all included studies was performed. In only five of ten studies an endometrial biopsy was performed during treatment. All of these studies described specific histological non-physiological endometrial changes (PAEC) due to ulipristal acetate, varying from 41 to 78.8% of all patients. Three of these studies also performed follow-up biopsies after discontinuing ulipristal acetate. The percentage of PAEC decreased from 62% to 0%, 78.8% to 0% and from 59% to 6-7% after the treatment period. In six of 1450 women (0.4%) endometrial

  1. Evaluation of Prognostic Factors Following Flow-Cytometric DNA Analysis after Cytokeratin Labelling: II. Cervical and Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Pauline Wimberger

    2002-01-01

    Full Text Available In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S‐phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC‐conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17 prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA‐ploidy nor S‐phase fraction were relevant prognostic parameters. But CV of the G0G1‐peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA‐aneuploidy (DNA‐index > 1.3 and a high percentage of proliferating cells (>75th percentile were univariate and multivariate highly significant prognostic factors for recurrence‐free survival. Especially DNA‐aneuploidy (DI>1.3 is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA‐ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA‐ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA‐parameters was found.

  2. The Role of Vaginal Brachytherapy in the Treatment of Surgical Stage I Papillary Serous or Clear Cell Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barney, Brandon M., E-mail: barney.brandon@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Mariani, Andrea; Dowdy, Sean C.; Bakkum-Gamez, Jamie N. [Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota (United States); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2013-01-01

    Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic and paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.

  3. Vaginal cuff brachytherapy in endometrial cancer - a technically easy treatment?

    Science.gov (United States)

    Sabater, Sebastià; Andres, Ignacio; Lopez-Honrubia, Veronica; Berenguer, Roberto; Sevillano, Marimar; Jimenez-Jimenez, Esther; Rovirosa, Angeles; Arenas, Meritxell

    2017-01-01

    Endometrial cancer (EC) is one of the most common gynecological cancers among women in the developed countries. Vaginal cuff is the main location of relapses after a curative surgical procedure and postoperative radiation therapy have proven to diminish it. Nevertheless, these results have not translated into better survival results. The preeminent place of vaginal cuff brachytherapy (VCB) in the postoperative treatment of high- to intermediate-risk EC was given by the PORTEC-2 trial, which demonstrated a similar reduction in relapses with VCB than with external beam radiotherapy (EBRT), but VCB induced less late toxicity. As a result of this trial, the use of VCB has increased in clinical practice at the expense of EBRT. A majority of the clinical reviews of VCB usually address the risk categories and patient selection but pay little attention to technical aspects of the VCB procedure. Our review aimed to address both aspects. First of all, we described the risk groups, which guide patient selection for VCB in clinical practice. Then, we depicted several technical aspects that might influence dose deposition and toxicity. Bladder distension and rectal distension as well as applicator position or patient position are some of those variables that we reviewed.

  4. Improving antenatal risk assessment in women exposed to high risks.

    Science.gov (United States)

    Perry, Natasha; Newman, Louise K; Hunter, Mick; Dunlop, Adrian

    2015-01-01

    Antenatal substance use and related psychosocial risk factors are known to increase the likelihood of child protection involvement; less is known about the predictive nature of maternal reflective functioning (RF) in this population. This preliminary study assessed psychosocial and psychological risk factors for a group of substance dependent women exposed to high risks in pregnancy, and their impact on child protection involvement. Pregnant women on opiate substitution treatment (n = 11) and a comparison group (n = 15) were recruited during their third trimester to complete measures of RF (Pregnancy Interview), childhood trauma, mental health and psychosocial assessments. At postnatal follow-up, RF was reassessed (Parent Development Interview - Revised Short Version) and mother-infant dyads were videotaped to assess emotional availability (EA). Child protection services were contacted to determine if any concerns had been raised for infant safety. Significant between-group differences were observed for demographics, psychosocial factors, trauma and mental health symptoms. Unexpectedly, no significant differences were found for RF or EA between groups. Eight women in the 'exposed to high risks' group became involved with child protection services. Reflective functioning was not significantly associated with psychosocial risk factors, and therefore did not mediate the outcome of child protection involvement. Women 'exposed to high risks' were equally able to generate a model of their own and their infants' mental states and should not be seen within a deficit perspective. Further research is required to better understand the range of risk factors that predict child protection involvement in high risk groups. © The Author(s) 2013.

  5. Surgical staging in endometrial cancer

    NARCIS (Netherlands)

    Mourits, MJ; Aalders, JG; Slager, E; Fauser, B; VanGeijn, H; Brolmann, H; Vervest, H

    2005-01-01

    Endometrial cancer is the most prevalent cancer of the female genital tract. No randomised study exists to prove that pelvic and para-aortic lymphadenectomy increases survival, either by dissecting micrometastases or by altering the adjuvant treatment in all early stage (stage I grade I and 2)

  6. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  7. The high-risk plaque initiative

    DEFF Research Database (Denmark)

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter

    2011-01-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies...

  8. High risk of permafrost thaw

    Energy Technology Data Exchange (ETDEWEB)

    Schuur, E.A.G.; Abbott, B.; Koven, C.D,; Riley, W.J.; Subin, Z.M.; al, et

    2011-11-01

    In the Arctic, temperatures are rising fast, and permafrost is thawing. Carbon released to the atmosphere from permafrost soils could accelerate climate change, but the likely magnitude of this effect is still highly uncertain. A collective estimate made by a group of permafrost experts, including myself, is that carbon could be released more quickly than models currently suggest, and at levels that are cause for serious concern. While our models of carbon emission from permafrost thaw are lacking, experts intimately familiar with these landscapes and processes have accumulated knowledge about what they expect to happen, based on both quantitative data and qualitative understanding of these systems. We (the authors of this piece) attempted to quantify this expertise through a survey developed over several years, starting in 2009. Our survey asked experts what percentage of surface permafrost they thought was likely to thaw, how much carbon would be released, and how much of that would be methane, for three time periods and under four warming scenarios that are part of the new IPCC Fifth Assessment Report.

  9. High risk pregnancy monitored antenatally at home

    NARCIS (Netherlands)

    Monincx, W. M.; Zondervan, H. A.; Birnie, E.; Ris, M.; Bossuyt, P. M.

    1997-01-01

    OBJECTIVE: Is domiciliary antenatal fetal surveillance for selected high risk pregnancies, a feasible alternative for hospital admission? DESIGN: A randomized controlled trial conducted at the Academical Medical Centre, Amsterdam, The Netherlands. SUBJECTS: Between September 1992 and June 1994, 76

  10. Feasibility of endometrial assessment after thermal ablation.

    Science.gov (United States)

    Ahonkallio, Sari J; Liakka, Annikki K; Martikainen, Hannu K; Santala, Markku J

    2009-11-01

    To evaluate the feasibility of endometrial assessment after endometrial thermal ablation. Prospective observational study. A total of 57 women (age 47-52 years), who had undergone endometrial thermal ablation as a treatment for heavy menstrual bleeding (HMB) 3-10 years (mean 6 years) earlier, were examined with transvaginal ultrasound and saline sonohysterography. Endometrial samples were collected with a Pipelle device. Visualisation of endometrium, access to uterine cavity, change in cavity length, success in outpatient endometrial sampling and success in sonohysterography were evaluated. Endometrial thickness was 4.5mm in amenorrhoeic women (n=17), 5.6mm in eumenorrhoeic women (n=37) and 6.6mm in hypermenorrhoeic women (n=3). An endometrial sample was successfully taken in 44 (77%) women, and in 13 (23%) women endometrial sample taking failed. The length of the uterine cavity compared to the length measured before endometrial thermal ablation was 0.5-5 cm (mean 2 cm) shorter in 34 women, unchanged in four women and longer in five women. The uterine cavity distended regularly in only nine (16%) women. In 14 (25%) women the cavity distended irregularly or only partly, and in 24 (42%) women the uterine cavity did not distend at all, but appeared as a narrow tube. In 10 (18%) women the sonohysterography catheter did not enter the uterine cavity at all. Endometrial assessment is compromised after previous endometrial thermal ablation. Both endometrial sampling and sonohysterography fail quite often, causing problems in diagnosis of abnormal bleeding. Intrauterine adhesions may also decrease the reliability of the endometrial sampling.

  11. Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

    Science.gov (United States)

    Shafiee, Mohamad N; Mongan, Nigel; Seedhouse, Claire; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, Willia