Presence Of Endometrial Cancer Research Articles

The Possible Role of Mycotoxins in the Pathogenesis of Endometrial Cancer

Endometrial cancer is one of the most common cancer types among women. Many factors can contribute to the development of this disease, including environmental factors and, thus, eating habits. Our study aims to determine the levels of various mycotoxins and their metabolites in the blood serum and endometrial tissue samples of participants with previously proven endometrial cancer and to find possible contributions to cancer development. In the cohort clinical trial, 52 participants aged between 44 and 86 were studied. The participants were divided into two groups: patients or matched controls. All patients had previously histologically diagnosed endometrial cancer. The cancer patients were divided into low-grade endometrioid and low- plus high-grade endometrioid groups. Controls had no history of endometrial malignancy or premalignancy. Blood serum and endometrial tissue samples were obtained from all study patients. We compared the concentrations of total Aflatoxins (Afs), Deoxynivalenol (DON), Ochratoxin-A (OTA), T2-toxin and HT2 toxin (T2/HT2 toxin), Zearalenone (ZEN), alpha-Zearalenol (α-ZOL), and Fumonisin B1 (FB1) in the serum and endometrium between the different study groups. As a result, we can see a significant correlation between the higher levels of Afs and zearalenone and the presence of endometrial cancer. In the case of Afs, DON, OTA, T2/HT2 toxins, ZEN, and alpha-ZOL, we measured higher endometrial concentrations than in serum. Considering the effect of mycotoxins and eating habits on cancer development, our results might lead to further research exploring the relationship between certain mycotoxins and endometrium cancer.

Patients with endometrial intraepithelial neoplasia do not need routine lymph node sampling

<h3>Objectives:</h3> The use of sentinel lymph node (SLN) protocols in endometrial cancer has emerged as a standard of care for staging invasive endometrial cancers, while in endometrial intraepithelial neoplasia (EIN), their role is not well defined. We sought to identify preoperative characteristics that may predict the presence of concurrent endometrial cancer at the time of hysterectomy in order to identify who may benefit from nodal assessment at the time of hysterectomy. <h3>Methods:</h3> Using billing codes for EIN or complex endometrial hyperplasia, we identified all patients with a pre-operative diagnosis of EIN from 2010 through 2020. Those who subsequently underwent surgical management (i.e. minimally invasive or open hysterectomy±adnexal surgery and±lymph node dissection) were included in this analysis. Patients were excluded if they opted for medical management or if subsequent pathology review indicated an alternative preoperative diagnosis. Data was abstracted from medical records. Data are presented as n (%) and median (interquartile range); we used modified Poisson regression to calculate risk ratios (RR) and 95% confidence intervals (CI). <h3>Results:</h3> Of the 492 patients with a diagnosis of EIN, 378 patients underwent hysterectomy. Surgical pathology revealed 275 (73%) had EIN or no residual disease, and 103 (27%) had endometrial cancer. Age (p=0.003), race (p=0.02), and concurrent diagnosis of hypertension (p=0.02) were significantly associated with the presence of endometrial cancer on final pathology. Notably, the median preoperative endometrial thickness was significantly greater in the endometrial cancer group [14mm (10-19)] than in the EIN group [11mm (8-16); p=0.002]. When dichotomizing endometrial thickness, patients with a preoperative endometrial stripe ≥15mm were 1.77 times more likely to have endometrial cancer than those with an endometrial stripe <15mm (95% CI: 1.24-2.54). The corresponding RR for those with a preoperative endometrial stripe ≥20mm was 1.97 (95% CI: 1.34-2.90). A total of 5 patients (1.3%) were diagnosed with stage IB (>50% myometrial invasion) disease, 30 (8%) patients had tumors > 2cm, 1 (0.3%) had grade 3 histology, and 3 (0.8%) had lymphovascular space invasion (LVSI). In this cohort, only 10 (3%) of patients underwent lymph node evaluation at time of surgery based on intra-operative factors, including frozen section. <h3>Conclusions:</h3> In a large cohort of patients with a preoperative diagnosis of EIN, 27% were found to have invasive carcinoma, but very few patients had pathologic features portending increased risk of nodal metastasis. Even fewer met intraoperative criteria for lymph node evaluation. Increasing endometrial thickness may be a useful pre-operative marker to identify who is at higher risk for concurrent endometrial cancer and could be considered a criterion for use of a sentinel lymph node algorithm in patients with EIN. Prospective studies are warranted.

Dolor abdominal autolimitado

&lt;p&gt;El dolor abdominal es un síntoma inespecífico y puede tener un origen sensitivo, visceral o sistémico. La evaluación del paciente con dolor abdominal puede ser un reto debido a hallazgos clínicos no concluyentes, lo que conduce a un diagnóstico incorrecto. En el presente escrito se aborda el caso de una paciente femenina de 77 años que presentaba dolor abdominal difuso, persistente, de largo tiempo de evolución, sin respuesta a tratamiento. Después de múltiples visitas médicas se detecta una masa no específica en hemiabdomen inferior izquierdo; estudios histopatológicos refieren la presencia de cáncer de endometrio.&lt;/p&gt;

Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study.

To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

Silencing of angiotensin receptor 1 interferes with angiotensin II oncogenic activity in endometrial cancer.

In mammalian cells, angiotensin II (AngII) binds to 2 distinct high-affinity plasma membrane receptors: angiotensin receptor 1 (AT1R) and angiotensin receptor 2 (AT2R). Healthy human endometrium from women of reproductive age expresses all of the components of the renin-angiotensin system. Many studies suggest that AngII, acting via AT1R, may have a role in the development and progression of cancer, which changesthe expression of angiogenic factors, AngII and AT1R are correlated with the presence of endometrial cancer (EC). The aim of the current study was to identify the effects of AngII on the proliferation, cell cycle progression, apoptosis and mobility of ISHIKAWA, MFE296 and MFE280 EC cells with silenced AT1R. It also examines epithelial-mesenchymal transition markers by gene expression analysis. The obtained results suggest that the silencing of AT1R expression alters the migration and invasion ability of EC cells. However, this silencing is not sufficient to inhibit the effects of AngII on EC cells, suggesting that AngII plays a more complex role in the development of EC.

Evaluation of biologically active substances promoting the development of or protecting against endometrial cancer.

IntroductionAdipose tissue is considered an endocrine organ and produces a number of biologically active substances.AimsTo consider the role that four adipokines – leptin, omentin-1, vaspin, and galectin-3 – play in the diagnosis of endometrium cancer and to investigate the association between serum concentrations of adipose tissue metabolism products and the diagnostics and prognosis in endometrial cancer.Patients and methodsThe study included 168 patients with body mass index (BMI) >20 kg/m2 admitted due to post-menopausal bleeding.ResultsA receiver operating characteristic curves test was performed to determine the diagnostic values of the proteins tested. For leptin and galectin-3 the area under the curve (AUC) values were 0.79/0.68, while for vaspin and omentin-1 the AUC values were 0.82/0.86 for all study patients. The final model identified the following independent risk factors: glucose concentration, BMI, waist circumference, leptin, and vaspin concentrations. Diagnostic values of leptin and galectin-3 with regard to differentiation between high (Fédération Internationale de Gynécologie Obstétrique [FIGO] III and IV) and low (FIGO I and II) stages of clinical tumor advancement and prediction of tumor grading (G1 vs G3) based on the AUC curve were 0.82/0.70 and 0.80/0.74. The AUC values for vaspin and omentin-1 with respect to differentiation between histopathological advancement and grading were 0.86/0.81 and 0.83/0.77, respectively. Significantly lower values of mean omentin-1 and vaspin concentrations were also demonstrated in cases of lymphatic vessel invasion, lymph node metastases, or deep endometrial infiltration (p=0.002, p=0.01, p=0.003, respectively).ConclusionIt appears that elevated concentrations of leptin, vaspin, and omentin-1 may indicate the presence of endometrial cancer. Furthermore, leptin serum level and vaspin appear to be useful tools in the assessment of clinical staging of endometrial cancer.

Potential contribution of the uterine microbiome in the development of endometrial cancer.

BackgroundEndometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer.MethodsWe undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17), patients with endometrial hyperplasia (endometrial cancer precursor, n = 4), and patients afflicted with benign uterine conditions (n = 10). Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq) of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and β-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model.ResultsThe microbiome sequencing (16S rDNA V3-V5 region) revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries) are significantly correlated (p < 0.001) and that there is a structural microbiome shift in the cancer and hyperplasia cases, distinguishable from the benign cases (p = 0.01). Several taxa were found to be significantly enriched in samples belonging to the endometrial cancer cohort: Firmicutes (Anaerostipes, ph2, Dialister, Peptoniphilus, 1–68, Ruminococcus, and Anaerotruncus), Spirochaetes (Treponema), Actinobacteria (Atopobium), Bacteroidetes (Bacteroides and Porphyromonas), and Proteobacteria (Arthrospira). Of particular relevance, the simultaneous presence of Atopobium vaginae and an uncultured representative of the Porphyromonas sp. (99 % match to P. somerae) were found to be associated with disease status, especially if combined with a high vaginal pH (>4.5).ConclusionsOur results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that should be further investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0368-y) contains supplementary material, which is available to authorized users.

Papillary Carcinoma in Mature Teratoma of Struma Ovarii

A 62-year-old woman had the incidental finding of malignant struma ovarii following surgery for primary endometrial carcinoma. The patient had vaginal bleeding for one year. After gynecological examination, she was referred for fractional curettage which revealed endometrial cancer. The patient underwent total hysterectomy and bilateral adnexectomy. Histological findings of uterus confirm the presence of endometrial cancer. The left ovary showed the presence of mature teratoma with dominant thyroid tissue and focus of papillary carcinoma. Postoperatively she underwent radiation therapy and 3 months later total thyroidectomy. The stimulated thyroglobulin level was detectable. She was referred for radioiodine ablation with a dose of 3,7GBq 131-J. Post therapy scintigraphy shows pathological uptake of 131-J only in the neck. The patient continued treatment of endometrial cancer (external beam therapy). She is currently on suppressive hormone L-thyroxin therapy. Two months later hormonal status, thyroglobulin and antithyroglobulin antibodies showed optimal range.

Structured Hysteroscopic Evaluation of Endometrium in Women With Postmenopausal Bleeding.

To evaluate visual pattern parameters obtained with hysteroscopy for the prediction of endometrial cancer, to evaluate observer variation of these parameters, and to present a scoring system of the parameters for the prediction of malignancy compared with subjective evaluation. A prospective controlled study (Canadian Task Force classification II-1). A university clinic. One hundred forty-nine consecutive women with postmenopausal bleeding and an endometrium thickness ≥ 5 mm. Sixty-one (41%) had endometrial cancer. Forty-six of 149 women were referred based on suspected malignancy. Endometrial pattern characteristics for endometrial cancer were evaluated in hysteroscopic video clips. The reference standard was pathologic evaluation of resectoscopic samples or hysterectomy. Using multivariate logistic regression, image parameters were correlated with the presence of endometrial cancer. A scoring system of visual parameters for the prediction of malignancy was compared with subjective evaluation of malignancy. A score for lesion surface, necrosis, and vessels had an area under the curve (AUC) of 0.89, 0.89, and 0.87, respectively. A hysteroscopic cancer (HYCA) scoring system based on unsmooth lesion surface, papillary projections, surface necrosis, "candy floss" necrosis, white hyperintense spots, irregular branching vessels, and irregular distribution of irregular vessels was able to predict cancer (AUC = 0.964) with higher accuracy than subjective evaluation (AUC = 0.859, p < .01). At a score value ≥ 3, sensitivity was 89% and specificity was 92% with moderate agreement between observers (kappa = 0.56 [0.42-0.71]). A systematic pattern evaluation of optimal parameters by a HYCA scoring system based on systematically defined terms may increase accuracy in the diagnosis of endometrial cancer and should be further elaborated and external validity tested in unselected women with postmenopausal bleeding.

EFICIENCIA DE LOS MÉTODOS DIAGNÓSTICOS EN EL ESTUDIO DEL SANGRADO UTERINO ANORMAL EN LA PERI Y POSTMENOPAUSIA

SUMMARY Abnormal uterine bleeding is an important symptom that can mean presence of endometrial cancer or endometrial hyperplasia. The aim of this study is to assess the effectiveness of selected diagnostic methods in peri and potmenopausal women with abnormal uterine bleeding, and to propose a way to manage in these patients. Different diagnostic methods are assessed, which include transvaginal ultrasonography, sonohysterography, Doppler technique, magnetic resonance images, biopsy by Pipelle, dilatation and curettage, and hysteroscopy. It is founded that ultrasonography has a high efficiency when it comes for identifying diffuse lesions, while sonohysterography has a high efficiency for identify focal lesions. On the other hand biopsy by Pipelle has demonstrated to rule out diffuse pathology with a high efficiency. It is concluded that the best way to manage patients with abnormal uterine bleeding by performing ultrasonography and sonohysterography at the same time followed by a Pipelle biopsy. Finally, it can be suggested that by this way it is highly probable that all cases with endometrial carcinoma and endometrial hyperplasia can be identified.

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

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

Refining the Amsterdam Criteria and Bethesda Guidelines: Testing Algorithms for the Prediction of Mismatch Repair Mutation Status in the Familial Cancer Clinic

Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.

Body fat distribution as a risk factor of endometrial cancer.

To investigate the relative contributions of upper body fat distribution and overall adiposity to endometrial cancer risk. Subjects were 63 postmenopausal women with endometrial cancer aged less than 70 years and 201 age-matched controls. Age, age at menopause, years since menopause, height, weight, and body mass index were recorded at the time of admission. The trunk-leg fat ratio, body fat mass, trunk fat mass, and the percentage of body fat were measured by dual-energy X-ray absorptiometry. Trunk-leg fat ratio was higher in endometrial cancer patients than in controls (1.40 +/- 0.59 vs 1.23 +/- 0.39, p < 0.05). Whereas, other variables including age at menopause, percentage of body fat, body fat mass, and body mass index did not differ between the 2 groups. On stepwise multiple regression analysis, the trunk-leg fat ratio was still correlated with the presence of endometrial cancer (p < 0.05). Upper body fat distribution rather than overall adiposity is associated with endometrial cancer risk.

Bone mineral density in postmenopausal women with endometrial cancer

Objective: The aim of the study was to investigate the relationship between endometrial cancer and bone mineral density (BMD). Materials and methods: A total of 55 postmenopausal Japanese women with well-differentiated adenocarcinoma and 284 age-matched healthy women were studied. Baseline characteristics including age, age at menopause, years since menopause (YSM), weight, height, body mass index (BMI), prior menstrual history, parity, and fertility were recorded for each subject. Lumbar spine BMD (L2-4), and body fat indices including body fat mass amount and percent body fat were measured by dual-energy X-ray absorptiometry. These variables were compared between the two groups. In all subjects ( n=339), correlations of BMD with the presence of endometrial cancer, baseline characteristics, and body fat indices were investigated, using univariate and multiple regression analyses. Results: BMD, weight, BMI, body fat mass amount, and percent body fat were significantly higher in women with endometrial cancer. Other baseline characteristics did not differ between the two groups. Age at menopause, height, weight, BMI, percent body fat, and body fat mass amount were positively correlated with BMD, while age and YSM were inversely correlated with BMD. After adjusting for age, YSM, and height, the presence of endometrial cancer was still correlated with BMD ( P<0.05). However, after adding body fat mass amount to these three adjusted variables, there was no correlation between the presence of endometrial cancer and BMD. Conclusion: Women with endometrial cancer have a high BMD. This is attributable to high body fat mass amount in this disease.

A Significant Correlation between Melatonin Deficiency and Endometrial Cancer

Endometrial cancer is the most common pelvic genital cancer in women. Its incidence is increasing. Unlike the successful screening method for cervical cancer, there is no such equivalent procedure for the early diagnosis of endometrial cancer. Screening procedures currently being tested are too insensitive and nonspecific while diagnostics are either too complex or invasive. In Austria, a multicenter study was begun to search for parameters appropriate for a screening program. 138 women were selected based on anamnestic, serologic and cytologic risk factors. 68 women were diagnosed with endometrial cancer, 70 patients had abnormal bleeding. There were no significant differences in age and menopausal status. Secondary diseases including diabetes mellitus, hypertonia and adipositas were evenly distributed in both groups. In addition to the routine hormone analyses, we tested the patients’ plasma for differences in melatonin levels. We found a significant correlation (p < 0.001) between melatonin plasma levels and the presence of endometrial cancer. The mean plasma melatonin value was 6.1 pg/ml in the cancer-positive group and 33.2 pg/ml in the cancer-negative control group resulting in a 6-fold difference between the two groups. We conclude that decreasing melatonin plasma levels may be an indicator of endometrial cancer and that this may therefore be used as a reliable screening parameter.

Uterine prolapse complicated by endometrial cancer

Objective: An infrequent clinical dilemma arises when a patient with uterine prolapse that is best treated vaginally is discovered to have coexisting endometrial cancer. Often the underlying cancer is only discovered intraopertively or postoperatively. We have reviewed our experience in this situation in an effort to evaluate efficacy of treatment, strategies to avoid late postoperative discovery of cancer, and general guidelines for optimal treatment. Study design: At the Mayo Clinic from 1950 to 1993, 54 patients with coexisting endometrial carcinoma underwent vaginal hysterectomy with repairs for uterine prolapse. Results: We have restrospectively reviewed these cases for relevant data and survival analysis. Complete follow-up is available for 53 patients bilateral oophorectomy was not performed for multiple reasons, and one of these patients had a recurrence. Twenty-five percent of all patients had disease confined to the endometrium, and 80% overall had low-grade lesions with superficial or no myometrial invasion. Of the four recurrences, three would have been considered low risk of extrauterine spread, and it is doubtful that an abdominal approach would have yielded additional useful information. No patient required reoperation for recurrent pelvic relaxation. Conclusion: We believe that for certain selected patients vaginal surgery for uterine prolapse is adequate treatment in the presence of endometrial cancer. We discuss the selection strategies, exclusion criteria, and general guidelines to optimize care for these challenging patients. 1995; 172; 1675–1683.)

The conversion of androstenedione to oestrone and production of oestrone in women with endometrial cancer

The conversion of androstenedione to oestrone and the production rate of oestrone has been measured in a group of women with endometrial cancer. In four postmenopausal subjects, conversion of androstenedione to oestrone ([ ρ] BU AE 1 = 2.1 ± 0.7%, mean ± S.D.) and the production rate of oestrone (26.8 ± 5.7 μg/24 h) were not excessive and similar to that reported for normal postmenopausal women. No significant change in either the extent of the conversion of androstenedione to oestrone or the production rate of oestrone was found when the postmenopausal women were re-investigated 2–3 months after ovariectomy and hysterectomy. For one premenopausal woman with endometrial cancer, conversion of androstenedione to oestrone ([ ρ] BU AE 1 = 1.5%) and production of oestrone (63.4 μg/24h) were within the ranges reported for normal premenopausal women. A significant negative correlation ( r = −0.76, P < 0.02) was found between the plasma production rate of androstenedione and the conversion of androstenedione to oestrone. From this study it was concluded that the presence of endometrial cancer in these subjects was not associated with increased production of oestrone or conversion of androstenedione to oestrone and that the conversion of androstenedione to oestrone depends in part on the plasma production rate of androstenedione.