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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.

The review discusses the efficacy and safety of phytoestrogens, preferably soy isoflavones in treating the menopausal syndrome symptoms. Particular attention is paid to the synthetic genistein. The highest genistein efficacy, when compared to other phytoestrogens is confirmed by comparative and placebo-controlled trials. However, prolonged use of genistein does not affect the proliferate processes in the endometrium and breast. Genistein can be considered a good alternative to hormone therapy when it is proved to be impossible or undesirable.

The article discusses the use of valproate and clozapine during course of chemoradiation in a 78-year-old White female with malignancy. Highlights include a total abdominal hysterectomy with bilateral salpingo-oophorectomy underwent by the patient, the overall nadir of her absolute neutrophil count, and the adjunctive use of valproate to treat schizoaffective disorder in the case of the patient.

Background: Endometrial cancer is the most common type of malignancy in female reproductive system and is the fourth common cancer after breast, lungs and colorectal cancers. Our aim is to report epidemiology and frequency types of endometrial cancer and clinical staging and grading of this disease. Methods: In this description and Cross-Sectional study, 75 patients with diagnosed endometrial cancer, being admitted to surgical ward of Rouhani Hospital or Shahid rajaii Hospital in Iran were enrolled to study. Demographic specification of patient, staging and grading and other variables related with endometrial cancer were collected and data was processed by SPSS version 18 software. Results: Disease of diabetes, hypertension and obesity had a frequency of 36%, 26.7% and 85.3% in orderly. The mean of abortion was 0.47, mean of delivery was 3.71, mean age of menarche was 13.73 and most frequent age of first delivery belonged to the range of 19-24 year old (47ones, 62.7%). A high percentage of patients had been menopause under 39 years of age (25 ones, 33.3%). 3 patients (4%) had a history of breast cancer and usage of Tamoxifen. Only 6 cases (8%) had a history of irregularities menstruation. 58 of patients were in stage1 and 17 were other stages. 77.2% of patients have endometrioid and 13 patients were suffered by sarcoma. Conclusion: Most patients with endometrial cancer had endometrioid. Times of delivery and abortion, lower age of menarche and age of menopause and at the first delivery have been appeared to be associated with endometrial cancer.

Introduction: Abnormal Uterine Bleeding (AUB) is most common gynaecological problem but its management is not well defined. So FIGO/PALMCOEIN classification was developed to provide clear management options as treatment is different in PALM and AUB-E group. FIGO/PALM-COEIN classification and immunohistochemistry with ERα and PR expression in AUB-E group will be helpful in management of these patients, thus preventing surgical interventions. Aim: To study histomorphological classification according to FIGO/PALM-COEIN classification in patients presenting with AUB into PALM and AUB-E group. To study the receptor expression of ERα and PR in AUB-E group. Materials and Methods: This cross sectional study was performed in patients presenting with AUB in reproductive age group (15-45 years). Six hundred endometrial specimens were stained with H&E for histolomorphological examination and classified as per FIGO/PALM-COEIN classification of AUB in non-gravid women in reproductive age group. Fifty endometrial biopsies were of pregnancy and pregnancy related complications and were excluded from study. A total of 550 samples were evaluated in present study. IHC for quantification of ERα and PR expression was carried out in AUB-E (100) cases and control group endometrium (20) cases due to technical constraints. Statistical Analysis: Unpaired student t-test was performed. p-value ≤ 0.05 was taken as critical level of significance. Results: Endometrial (58.19%) (AUB-E) causes were most common cause of AUB. Most common morphology was AUB-E (Proliferative endometrium), AUB-L (Leiomyoma) and AUB-E (Secretory endometrium) respectively. Statistically significant expression of ERα and PR was found in AUB-E endometrium as compared to control group endometrium. In Non secretory/ Proliferative endometrium AUB-E group. Proliferative endometrium and hyperplasia without atypia had significant expression of ERα and PR in glands and stroma when compared with proliferative phase control group endometrium. But disordered proliferative endometrium had only significant PR expression in stroma. When secretory phase endometrium was compared with control group secretory phase significant expression for PR was noted only in stroma. Conclusion: FIGO/PALM-COEIN classification will be helpful in deciding treatment of AUB cases. Study of receptor expression in AUB-E group will help in providing evidence based treatment and prevent from surgical procedures like hysterectomy and endometrial ablation.

Population-level cancer incidence rates are one measure to estimate the cancer burden. The goal is to provide information on trends to measure progress against cancer at the population level and identify emerging patterns signifying increased risk for additional research and intervention. Endometrial cancer is the most common of the gynecologic malignancies but capturing the incidence of disease among women at risk (i.e. women with a uterus) is challenging and not routinely published. Decreasing rates of hysterectomy increase the number of women at risk for disease which should be reflected in the denominator of the incidence rate calculation. Furthermore hysterectomy rates vary within the United States by multiple factors including geographic location, race and ethnicity. Changing rates of hysterectomy are important to consider when looking at endometrial cancer trends. By correcting for hysterectomy when calculating incidence rates of cancers of the uterine corpus, many of the disparities that have been assumed for this disease are diminished.

Hereditary cancers breast, ovarian, and endometrial cancers comprise a significant portion of cancers affecting women. This paper strives to review the genetics and current screening, prophylaxis, and treatment of these malignancies.

Background The purpose of this study was to examine the rate and clinico-Pathological characteristics of ovarian metastasis of endometriod type endometrial cancer. Materials and Methods A retrospective study of all patients with endometriod type endometrial cancer was carried out during 1990-2009. Chi-square and Fisher’s Exact tests were used to analyze all the variables. P ≤ 0.05 was considered statistically significant. SPSS software (version 18), was used for statistical analysis of the data obtained. Results Two hundred and ten patients fulfilled the inclusion criteria. Only 17 (8%) cases were identified to have ovarian metastasis. Fisherُ s Exact test showed that the independent risk factors of ovarian metastasis in endometrial carcinoma included pathologic grading and depth of myometrial invasion (p < 0.001 and p < 0.02, respectively). Conclusion The risk of ovarian metastasis in the patients with well to moderately differentiated endometriod type endometrial cancer and myometrial invasion limited to less than one half of the myometrium is minimal. Therefore, it is possible to preserve ovaries in young women with early stage endometrioid type endometrial carcinoma, but it is better to remove and freeze ovarian tissue to save fertility without the recurrence risk of ovarian cancer.

While existing literature suggests an association between polycystic ovarian syndrome (PCOS) and endometrial cancer, the sparsity and inconsistency of current evidence indicates a lack of clarity regarding the exact strength of this association. It also remains uncertain whether the degree of risk of disease is affected by confounding factors, such as age and body mass index (BMI). The present meta-analysis is aimed to quantify the risk of endometrial cancer in female subjects with PCOS compared to those without PCOS. PubMed, MEDLINE, EMBASE, Scopus and Cochrane were searched from inception to October 31, 2022, to identify peer-reviewed case-control, cohort and cross-sectional studies that assessed the association between endometrial cancer and PCOS and contained original data. Two researchers independently extracted data and performed quality assessment using the Newcastle-Ottawa criteria. Pooled odds ratios (ORs) were calculated using the random-effect model and inverse variance. The degree of heterogeneity was assessed using I2 statistics. A total of 10 relevant studies were identified and included in the meta-analysis (comprising 12,248 female patients with PCOS and 54,120 controls). Females with PCOS had a significantly increased odds of developing endometrial cancer as compared to those without PCOS [OR, 4.07; 95% confidence interval (CI), 2.13-7.78; P<0.0001]. When postmenopausal subjects (age, >54 years) were excluded from the meta-analysis, the odds increased further (OR, 5.14; 95% CI, 3.22-8.21; P<0.00001). Patients with PCOS are up to 5 times more likely to develop endometrial cancer compared to those without PCOS. Larger, prospective studies that are well-controlled for confounding factors, such as BMI, are required. [ABSTRACT FROM AUTHOR]

Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

Purpose: To provide a systematic review of the applications of 3D printing in gynecological brachytherapy., Methods: Peer-reviewed articles relating to additive manufacturing (3D printing) from the 34 million plus biomedical citations in National Center for Biotechnology Information (NCBI/PubMed), and 53 million records in Web of Science (Clarivate) were queried for 3D printing applications. The results were narrowed sequentially to, (1) all literature in 3D printing with final publications prior to July 2022 (in English, and excluding books, proceedings, and reviews), and then to applications in, (2) radiotherapy, (3) brachytherapy, (4) gynecological brachytherapy. Brachytherapy applications were reviewed and grouped by disease site, with gynecological applications additionally grouped by study type, methodology, delivery modality, and device type., Results: From 47,541 3D printing citations, 96 publications met the inclusion criteria for brachytherapy, with gynecological clinical applications compromising the highest percentage (32%), followed by skin and surface (19%), and head and neck (9%). The distribution of delivery modalities was 58% for HDR (Ir-192), 35% for LDR (I-125), and 7% for other modalities. In gynecological brachytherapy, studies included design of patient specific applicators and templates, novel applicator designs, applicator additions, quality assurance and dosimetry devices, anthropomorphic gynecological applicators, and in-human clinical trials. Plots of year-to-year growth demonstrate a rapid nonlinear trend since 2014 due to the improving accessibility of low-cost 3D printers. Based on these publications, considerations for clinical use are provided., Conclusions: 3D printing has emerged as an important clinical technology enabling customized applicator and template designs, representing a major advancement in the methodology for implantation and delivery in gynecological brachytherapy., (Copyright © 2023. Published by Elsevier Inc.)

French recommendations for clinical practice Nice-Saint-Paul de Vence 2022-2023: histomolecular diagnosis of endometrial carcinomas The characterisation of endometrial carcinomas has been recently modified and enriched by molecular classification, the integration of which now impacts therapeutic decisions on whether adjuvant therapy should be administered or not in localized tumors, and influences treatment selection in advanced disease. Mandatory information includes histological type according to WHO 2020 classification, histological grade, hormone receptors status and molecular classification, the main new elements to provide being analysis of MMR proteins, p53 status and POLE status in selected cases. Sampling and preparation of material must be performed adequately to allow complete analysis. Numerous markers can be used to better define histological type, distinguish between primary lesion or metastases, or provide prognostic information. Determination of MMR/MSI profile is complex but well defined by guidelines that precisely describe techniques to be used and interpretation rules. Knowledge of POLE status is useful to guide therapeutic strategy, especially to consider de-escalation in stages I and II, in particular in case of high grade and/or p53 mutated tumors. This is why indications of POLE determination must be well defined. Finally, oncogenetics consultation is recommended in dMMR tumors (except in case or MLH1 promoter methylation) and in patients with evocative familial history., (Copyright © 2023 Elsevier Masson SAS. Tous droits réservés. All rights reserved.)

Objective To analyze the patterns of care regarding intensity modulated radiation therapy (IMRT) usage in the postoperative management of uterine cancer. Methods The National Cancer Database was queried to identify women with endometrial adenocarcinoma who underwent hysterectomy followed by external beam radiation between 2004–2012. Descriptive statistics were used to analyze IMRT usage with comparison via the Chi Square test. Overall survival was also compared between IMRT and three dimensional conformal radiation therapy. Multivariable logistic regression and multivariable Cox Regression were used to identify covariables that impact IMRT usage and improved survival respectively. Results 7839 women were included in this study. IMRT utilization increased from 1.9% in 2004 to 32.4% in 2012 (p < 0.001). The adjusted odds ratio (OR) for IMRT in 2012 compared with 2004 was 24.90, 95% CI 15.24–40.67 (p < 0.001). Aside from year, other predictors of IMRT usage on multivariate analysis were positive nodes, higher dose, private insurance and higher income. Black race was associated with lower IMRT usage compared to Whites with an OR of 0.60, 95% CI 0.44–0.81 (p = 0.001). IMRT was not associated with significantly increased survival (HR 0.86, 95% CI 0.73–1.01, p = 0.06). Black race and positive nodes were associated with decreased survival within the group studied whereas private insurance and higher income were associated with improved survival. Conclusions In this hospital-based registry, IMRT has significantly increased in utilization for postoperative radiation in uterine cancer between 2004–2012 although not resulting in significantly improved survival. Socioeconomic and racial disparities exist in the allocation of IMRT usage. [ABSTRACT FROM AUTHOR]

The incidence of most gynaecological malignancies rises significantly with increasing age. With an ageing population, the proportion of women over the age of 65 with cancer is expected to rise substantially over the next decade. Unfortunately, survival outcomes are much poorer in older patients and evidence suggests that older women with gynaecological cancers are less likely to receive current standard of care treatment options. Despite this, older women are under-represented in practice changing clinical studies. The evidence for efficacy and tolerability is therefore extrapolated from a younger; often more fit population and applied to in every day clinical practice to older patients with co-morbidities. There has been significant progress in the development of geriatric assessment in oncology to predict treatment outcomes and tolerability however there is still no clear evidence that undertaking a geriatric assessment improves patient outcomes. Clinical trials focusing on treating older patients are urgently required. In this review, we discuss the evidence for treatment of gynaecological cancers as well as methods of assessing older patients for therapy. Potential biomarkers of ageing are also summarised. [ABSTRACT FROM AUTHOR]

Purpose: A combination of the relatively high prevalence among gynecologic cancers, high survival, and the myriads of factors that negatively impact the quality of life (QoL) among endometrial cancer (EC) survivors underscores the potential benefits of meeting guideline physical activity (PA) guidelines of 150 minutes per week among EC survivors. The objective of the present systematic review was to collate and critically evaluate the currently available literature on the effects of PA on QoL among EC survivors. Methods: Medline and Web of Science databases were searched for articles on EC, QoL, and PA. We also inspected bibliographies of relevant publications to identify related articles. Our search criteria yielded 70 studies, 7 of which met the inclusion criteria. Results: Of the 7 studies examined, 2 of them were intervention studies, whereas 5 were cross-sectional studies. Meeting guideline PA was significantly associated with better QoL score in 4 of the 5 cross-sectional studies. Conclusions: Results from the cross-sectional studies suggest that EC survivors' inactivity is significantly correlated with poorer QoL. This correlation was worse among obese survivors compared with normal weight survivors. Endometrial cancer survivors may benefit from interventions that incorporate PA. More randomized intervention studies among EC survivors are needed to add to this body of evidence. [ABSTRACT FROM AUTHOR]

The emerging field of RNA nanotechnology has been used to design well-programmed, self-assembled nanostructures for applications in chemistry, biology, and medicine. At the forefront of its utility in cancer is the unrestricted ability to self-assemble multiple siRNAs within a single nanostructure formulation for the RNAi screening of a wide range of oncogenes while potentiating the gene therapy of malignant tumors. In our RNAi nanotechnology approach, V- and Y-shape RNA templates were designed and constructed for the self-assembly of discrete, higher-ordered siRNA nanostructures targeting the oncogenic glucose regulated chaperones. The GRP78-targeting siRNAs self-assembled into genetically encoded spheres, triangles, squares, pentagons and hexagons of discrete sizes and shapes according to TEM imaging. Furthermore, gel electrophoresis, thermal denaturation, and CD spectroscopy validated the prerequisite siRNA hybrids for their RNAi application. In a 24 sample siRNA screen conducted within the AN3CA endometrial cancer cells known to overexpress oncogenic GRP78 activity, the self-assembled siRNAs targeting multiple sites of GRP78 expression demonstrated more potent and long-lasting anticancer activity relative to their linear controls. Extending the scope of our RNAi screening approach, the self-assembled siRNA hybrids (5 nM) targeting of GRP-75, 78, and 94 resulted in significant (50-95%) knockdown of the glucose regulated chaperones, which led to synergistic effects in tumor cell cycle arrest (50-80%) and death (50-60%) within endometrial (AN3CA), cervical (HeLa), and breast (MDA-MB-231) cancer cell lines. Interestingly, a nontumorigenic lung (MRC5) cell line displaying normal glucose regulated chaperone levels was found to tolerate siRNA treatment and demonstrated less toxicity (5-20%) relative to the cancer cells that were found to be addicted to glucose regulated chaperones. These remarkable self-assembled siRNA nanostructures may thus encompass a new class of potent siRNAs that may be useful in screening important oncogene targets while improving siRNA therapeutic efficacy and specificity in cancer. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the most common type of malignancy of the female reproductive system and constitutes the fourth common cancer after breast, lungs and colorectal cancers. Our aim is to report the epidemiology and frequency of endometrial cancer as well as the clinical staging and grading of this disease. Methods: In this descriptive, cross-sectional study, 75 patients diagnosed with endometrial cancer, admitted to the surgical ward of Rouhani Hospital or Shahid Rajaii Hospital in Iran were enrolled. Demographic characteristics of patients, staging and grading and other variables related to endometrial cancer were collected and data was processed by SPSS version 18 software. Results: Diabetes, hypertension and obesity had frequencies of 36%, 26.7% and 85.3%, respectively. The mean count of abortion was 0.47, mean count of delivery was 3.71, mean age of menarche was 13.73 years and most frequent age of first delivery pertained to the range of 19-24 years old (n = 47, 62.7%). A high percentage of patients had entered menopause under 39 years of age (n = 25, 33.3%). Three patients (4%) had a history of breast cancer and using Tamoxifen. Only six cases (8%) had a history of irregularities menstruation. In total, 58 patients were in stage 1 and 17 were in other stages. Totally, 77.2% of patients have endometrioid and 13 patients suffered from sarcoma. Conclusions: Most patients with endometrial cancer had endometrioid. Time of delivery and abortion, lower age of menarche and age at menopause and at the first delivery appeared to be associated with endometrial cancer. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal Uterine Bleeding (AUB) is most common gynaecological problem but its management is not well defined. So FIGO/PALMCOEIN classification was developed to provide clear management options as treatment is different in PALM and AUB-E group. FIGO/PALM-COEIN classification and immunohistochemistry with ERα and PR expression in AUB-E group will be helpful in management of these patients, thus preventing surgical interventions. Aim: To study histomorphological classification according to FIGO/PALM-COEIN classification in patients presenting with AUB into PALM and AUB-E group. To study the receptor expression of ERα and PR in AUB-E group. Materials and Methods: This cross sectional study was performed in patients presenting with AUB in reproductive age group (15-45 years). Six hundred endometrial specimens were stained with H&E for histolomorphological examination and classified as per FIGO/PALM-COEIN classification of AUB in non-gravid women in reproductive age group. Fifty endometrial biopsies were of pregnancy and pregnancy related complications and were excluded from study. A total of 550 samples were evaluated in present study. IHC for quantification of ERα and PR expression was carried out in AUB-E (100) cases and control group endometrium (20) cases due to technical constraints. Statistical Analysis: Unpaired student t-test was performed. p-value ≤ 0.05 was taken as critical level of significance. Results: Endometrial (58.19%) (AUB-E) causes were most common cause of AUB. Most common morphology was AUB-E (Proliferative endometrium), AUB-L (Leiomyoma) and AUB-E (Secretory endometrium) respectively. Statistically significant expression of ERα and PR was found in AUB-E endometrium as compared to control group endometrium. In Non secretory/ Proliferative endometrium AUB-E group. Proliferative endometrium and hyperplasia without atypia had significant expression of ERα and PR in glands and stroma when compared with proliferative phase control group endometrium. But disordered proliferative endometrium had only significant PR expression in stroma. When secretory phase endometrium was compared with control group secretory phase significant expression for PR was noted only in stroma. Conclusion: FIGO/PALM-COEIN classification will be helpful in deciding treatment of AUB cases. Study of receptor expression in AUB-E group will help in providing evidence based treatment and prevent from surgical procedures like hysterectomy and endometrial ablation. [ABSTRACT FROM AUTHOR]

Objective A case control study of unexpected uterine sarcomas between laparoscopy and laparotomy was done to determine the influence of morcellation on the disease and to explore the early diagnosis by analyzing their characteristics. Methods Between November 2008 and November 2014, all of uterine sarcomas diagnosed after operation for benign uterine fibroid were abstracted and the patients were divided into two groups, laparoscopy (8 cases) or laparotomy (47 cases). Morcellator was used in laparoscopy, but not in laparotomy. The clinical datas were reviewed. Results The number of unexpected uterine sarcomas is 55 cases, 16 cases (7 laparoscopies and 9 laparotomies) underwent second surgery. Compared with laparotomy, laparoscopy had a higher risk of second surgery (87.5% vs. 19.1%, P=0.000) and pelvic planting and metastasis (2 cases vs. 0 case), and a lower rate of pathologic diagnosis (37.5% vs. 76.6%, P=0.038). Conclusions Laparoscopic morcellation had a higher risk of second surgery and pelvic planting and metastasis, and a lower rate of pathologic diagnosis. This should be paid more attention by clinicians and some measures should be taken to avoid the risk. [ABSTRACT FROM AUTHOR]

Purpose: Three-dimensional (3D) printing technology allows physicians to rapidly create customized devices for patients. We report our initial clinical experience using this technology to create custom applicators for vaginal brachytherapy. Material and methods: Three brachytherapy patients with unique clinical needs were identified as likely to benefit from a customized vaginal applicator. Patient 1 underwent intracavitary vaginal cuff brachytherapy after hysterectomy and chemotherapy for stage IA papillary serous endometrial cancer using a custom printed 2.75 cm diameter segmented vaginal cylinder with a central channel. Patient 2 underwent interstitial brachytherapy for a vaginal cuff recurrence of endometrial cancer after prior hysterectomy, whole pelvis radiotherapy, and brachytherapy boost. We printed a 2 cm diameter vaginal cylinder with one central and six peripheral catheter channels to fit a narrow vaginal canal. Patient 3 underwent interstitial brachytherapy boost for stage IIIA vulvar cancer with vaginal extension. For more secure applicator fit within a wide vaginal canal, we printed a 3.5 cm diameter solid cylinder with one central tandem channel and ten peripheral catheter channels. The applicators were printed in a biocompatible, sterilizable thermoplastic. Results: Patient 1 received 31.5 Gy to the surface in three fractions over two weeks. Patient 2 received 36 Gy to the CTV in six fractions over two implants one week apart, with interstitial hyperthermia once per implant. Patient 3 received 18 Gy in three fractions over one implant after 45 Gy external beam radiotherapy. Brachytherapy was tolerated well with no grade 3 or higher toxicity and no local recurrences. Conclusions: We established a workflow to rapidly manufacture and implement customized vaginal applicators that can be sterilized and are made of biocompatible material, resulting in high-quality brachytherapy for patients whose anatomy is not ideally suited for standard, commercially available applicators. [ABSTRACT FROM AUTHOR]

Purpose: The study assessed the outcomes of patients at a single institution with locally advanced primary and recurrent pelvic malignancies treated with interstitial high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy (BT), using a modified Syed-Neblett template. Material and methods: Between 1996 and 2010, 60 patients with primary or recurrent pelvic malignancies were treated with interstitial BT. Thirty three patients had primary malignancies with 6.1% being stage I, 33.3% stage II, 45.5% stage III, and 15.2% stage IV; the remaining 27 patients were recurrent malignancies. Fifty four patients received external beam radiotherapy (EBRT) as part of their treatment course. The median EBRT, BT, and EBRT + BT doses were 45 Gy, 20 Gy, and 65 Gy, respectively. Thirty eight patients received concurrent chemotherapy with EBRT. Complete response (CR) was defined by absence of clinical and radiographic disease on first follow-up. Toxicity was graded as per Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up was 37 months (4-234 months) and initial CR was achieved in 91%. For primary cancers at diagnosis, 5-year local control (LC), 5-year progression-free survival (PFS), 5-year overall survival (OS) were 65%, 64%, and 42% respectively. For recurrent cancers at diagnosis, 5-year LC, 5-year PFS, and 5-year OS were 80%, 51%, and 37%, respectively. There was a significant difference in both OS and PFS among different tumor sites (p < 0.05), with vaginal cancers having the best 5-year OS (55%) and PFS (84%). There was a total of 1 acute toxicity ≥ grade 3, 6 late grade 3 toxicities, and late grade 4 toxicity. Conclusions: Our series suggests that interstitial BT using a modified Syed-Neblett template is a safe and effective treatment for primary or recurrent pelvic malignancies. This technique allowed effective LC and 97% of patients had preservation of both bladder and rectal function. [ABSTRACT FROM AUTHOR]

Population-level cancer incidence rates are one measure to estimate the cancer burden. The goal is to provide information on trends to measure progress against cancer at the population level and identify emerging patterns signifying increased risk for additional research and intervention. Endometrial cancer is the most common of the gynecologic malignancies but capturing the incidence of disease among women at risk (i.e., women with a uterus) is challenging and not routinely published. Decreasing rates of hysterectomy increase the number of women at risk for disease, which should be reflected in the denominator of the incidence rate calculation. Furthermore, hysterectomy rates vary within the United States by multiple factors including geographic location, race, and ethnicity. Changing rates of hysterectomy are important to consider when looking at endometrial cancer trends. By correcting for hysterectomy when calculating incidence rates of cancers of the uterine corpus, many of the disparities that have been assumed for this disease are diminished. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study of 1,236 women, the rate (2.2%) of ectopic pregnancy was rare among women with a fluid collection (or pseudosac) in the uterus. The size of the fluid collection was not predictive of ectopic pregnancy. The presence of an intrauterine fluid collection decreased the risk of ectopic pregnancy (adjusted relative risk, 0.09; 95% confidence interval, 0.05-0.19) after adjusting for age and the presence of bleeding. [ABSTRACT FROM AUTHOR]

Una perra de la raza Bulldog fue atendida a los 3 años y 7 meses de edad con la siguiente historia clínica: primer celo a los 17 meses de edad y celos sucesivos en lapsos regulares cada 6 meses, fue inseminada con semen de un macho fértil, con base en el seguimiento por citología o la cuantificación de niveles séricos de progesterona, pero en ninguna ocasión quedó gestante (ecografía negativa entre los días 32 y 36 post-inseminación). Al día 6° del inicio del proestro del quinto celo se hizo examen ecográfico, se halló un quiste de 15 mm de diámetro y engrosamiento del endometrio. La perra fue sometida a laparotomía exploratoria, donde se halló hiperplasia bilateral de la mucosa de las fimbrias (de 10 mm de espesor, aproximadamente), aumento del diámetro de los oviductos y del cuello uterino, estructuras de 6 a 15 mm de diámetro que semejaban folículos en ambos oviductos, algunos translúcidos, unos de aspecto hemorrágico y otros de aspecto blanquecino. En los ovarios se hallaron estructuras compatibles con quistes, una de ellas la que se observó en la ecografía. En la mucosa uterina se hallaron múltiples quistes de 2 a 5 mm de diámetro. Se encontró esplenomegalia de la porción craneal y fibrosis de la porción caudal del bazo. La histopatología reveló una hiperplasia de las glándulas endometriales, engrosamiento de la mucosa del oviducto, salpingitis aguda y aumento de tejido graso de aspecto hemorrágico en el oviducto; en ambos ovarios se hallaron focos múltiples de tumores de células de la granulosa en patrón de células de empalizada (Sertoli) y quístico. En el bazo se halló esplenitis supurativa aguda y esclerosiderosis, un hallazgo compatible con hemorragias esplénicas debidas a estímulo estrogénico persistente. Los hallazgos se discuten en el contexto de una respuesta hiperestrogénica asociada con el tumor de las células de la granulosa y su posible relación con la historia de infertilidad en los celos anteriores. De conformidad con la información disponible en nuestro medio, el presente es el primer reporte en Colombia sobre tumor bilateral de células de la granulosa en perras.A case report of a 3 years and 7 months old Bulldog female dog with a history of infertility in four previous normal estrus cycles is presented. In all tour estrous the bitch was inseminated with fresh semen from a fertile Bulldog male, with a mating criteria based on cytology and progesterone levels results, without a successful pregnancy being diagnosed (negative pregnancy test by ultrasound at days 32 to 36 post-insemination). At the 6th day of the beginning of proestrus (of the 5th cycle) an ultrasound examination was performed to check for folicular ovarian activity, during which. Intra operatorium where several follicles ranging from 8 to 15 mm in diameter were found which suggested cystic structures. In addition, an endometrial thickening, and a non identified structure parallel to the left ovary were found, and then an exploratory laparotomy was decided. In the fimbriae a very strong bilateral hyperplasia of fimbrial mucosal was found (10 mm wide, approximately), and increased tubal and uterine cervix diameter. In both ovaries, several follicles ranking from 6 to 15 mm in diameter were found, some of they were of translucid aspect, another hemorrhagic, and others lutheinized. Multiple small (2 to 5 mm in diameter) cysts were found in the endometrium. Curiously, both a splenitis of the cranial and fibrosis of the caudal portions of the spleen were found. The histopathology report revealed fimbrial epitelial hiperplasia with acute salpingitis, and endometrial gland hyperplasia with cystic endometrial disease in the uterus. In the spleen, several sclerosiderosis foci, subcortical chronic hemorrhage, and acute supurative splenitis were found. In the ovaries a bilateral granulose cell tumor was diagnosed exhibiting a mixture of cystic and Sertoli cell patterns. These findings are discussed in the context of an granulose cell tumor-related hiperoestrogenic response and its relationship to the previous reproductive failure of the bitch. Accordingly, this is the first report on a bilateral granulosa cell tumor in dogs.

The latest WHO classification of the female genital tract tumors introduces a new type of carcinoma: the primary gastric-type (or gastro-intestinal type) carcinoma of the endometrium. This type of neoplasm tends to have a poor outcome, making its correct diagnostic important. As little is known about this entity and given its quite challenging diagnosis, we aim to review existing data about it and propose a practical diagnostic approach. There are currently 11 cases published in 8 articles fitting the precise definition of a primary gastric-type carcinoma of the endometrium. Three main differential diagnoses must be excluded before considering this tumor: endometrioid adenocarcinoma with mucinous (Müllerian-type) differentiation, endocervical primary, and gastro-intestinal primary. Morphological aspects of this tumor can be heterogeneous and confusing; in this context, immunochemistry can be helpful to highlight the gastric or intestinal differentiation, but also to eliminate a mucinous endometrioid adenocarcinoma of Müllerian-type, by the constant negativity of estrogen receptors. A metastasis of a primary gastro-intestinal tract carcinoma must also be excluded by clinical, endoscopic and imaging work-up. Finally, an endometrial extension of a primary endocervical gastric-type carcinoma should be ruled out by complete sampling of the cervix. Intestinal type endocervical adenocarcinoma is easier to eliminate since this is an HPV-associated neoplasm. [ABSTRACT FROM AUTHOR]

In the US, the incidence and mortality of many cancers are disproportionately higher in African Americans (AA). Yet, AA remain poorly represented in molecular studies investigating the roles that biological factors might play in the development, progression, and outcomes of many cancers. Given that sphingolipids, key components of mammalian cellular membranes, have well-established roles in the etiology of cancer progression, malignancy, and responses to therapy, we conducted a robust mass spectrometry analysis of sphingolipids in normal adjacent uninvolved tissues and tumors of self-identified AA and non-Hispanic White (NHW) males with cancers of the lung, colon, liver, and head and neck and of self-identified AA and NHW females with endometrial cancer. In these cancers, AA have worse outcomes than NHW. The goal of our study was to identify biological candidates to be evaluated in future preclinical studies targeting race-specific alterations in the cancers of AA. We have identified that various sphingolipids are altered in race-specific patterns, but more importantly, the ratios of 24- to 16-carbon fatty acyl chain-length ceramides and glucosylceramides are higher in the tumors of AA. As there is evidence that ceramides with 24-carbon fatty acid chain length promote cellular survival and proliferation, whereas 16-carbon chain length promote apoptosis, these results provide important support for future studies tailored to evaluate the potential roles these differences may play in the outcomes of AA with cancer.

Introduction: There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGO-ESTRO and their recommendations for adjuvant treatment have redefined the management protocols. In this retrospective analysis, the outcomes are assessed in the light of the new risk groups and FIGO staging., Material Methods: One hundred and two patients of endometrial cancer reporting to the Department of Radiation Oncology from 2015 to 2019 were analysed retrospectively. Patients were stratified as per the ESMO-ESGO-ESTRO risk groups and FIGO staging. Patients were analysed for demographic profile, histopathology details, FIGO stage, treatment modalities received as per the ESMO-ESGO-ESTRO risk groups and the outcomes in terms of disease free survival and overall survival., Results: A total of 102 patients were analysed. The mean age at presentation was 57.7 years. Seventy four percent (74.41%) were stage I patients, 14.7 % were stage II, 8.8% were stage III and remaining 2% were stage IV. The mean disease free survival for the patients in FIGO stage I, II, III and IV were found to be 63.5 (59.9 - 67) months, 60.5 (54.2 - 66.9) months, 30.9 (21.5 - 40.2) months and 15.4 (7.8 - 23.0) months respectively. The 5-year overall survival of patients in Stage I was 90.3%. The 3-year mortality of Stage III patients was 58.3%. While there was no mortality observed among Stage II patients, none of the Stage IV patient survived beyond 20 months. The 5-year disease-free survival for patients in Low Risk (LR) group, Intermediate Risk (IR) group and High Risk (HR) group was found to be 91.3%, 90% and 87% respectively. None of the patient in High Intermediate Risk (HIR) group experienced progression of disease and 33.3% patients in advanced group were disease free at 2 years follow-up. The multivariate analysis showed that lymph node involvement is significantly associated with disease-free (p=0.03) and overall survival (p=0.04)., Conclusion: Even in the developing world, majority of patients present in early stage with survival outcomes comparable to the West. FIGO stage and lymph node involvement continue to be the most important prognostic markers for disease outcomes., Competing Interests: None

Purpose: A new MRI parameter representative of active tumor burden is proposed: diffusion volume (DV), defined as the sum of all the voxels within a tumor with apparent diffusion coefficient (ADC) values within a specific range. The aims of the study were: (a) to calculate DV on ADC maps in patients with cervical/endometrial cancer; (b) to correlate DV with histological grade (G) and risk classification; (c) to evaluate intra/inter-observer agreement of DV calculation.Materials and Methods: Fifty-three patients with endometrial (n=28) and cervical (n=25) cancers underwent pelvic MRI with DWI sequences. Both endometrial and cervical tumors were classified on the basis of G (G1/G2/G3) and FIGO staging (low/medium/high-risk). A semi-automated segmentation procedure was used to calculate the DV. A freehand closed ROI outlined the whole visible tumor on the most representative slice of ADC maps defined as the slice with the maximum diameter of the solid neoplastic component. Successively, two thresholds were generated on the basis of the mean and standard deviation (SD) of the ADC values: lower threshold (LT="mean minus three SD") and higher threshold (HT="mean plus one SD"). The closed ROI was expanded in 3D, including all the contiguous voxels with ADC values in the range LT-HT × 10-3mm(2)/s. A Kruskal-Wallis test was used to assess the differences in DV among G and risk groups. Intra-/inter-observer variability for DV measurement was analyzed according to the method of Bland and Altman and the intraclass-correlation-coefficient (ICC).Results: DV values were significantly different among G and risk groups in both endometrial (p<0.05) and cervical cancers (p ≤ 0.01). For endometrial cancer, DV of G1 (mean ± sd: 2.81 ± 3.21 cc) neoplasms were significantly lower than G2 (9.44 ± 9.58 cc) and G3 (11.96 ± 8.0 cc) ones; moreover, DV of low risk cancers (5.23 ± 8.0 cc) were significantly lower than medium (7.28 ± 4.3 cc) and high risk (14.7 ± 9.9 cc) ones. For cervical cancer, DV of G1 (0.31 ± 0.13 cc) neoplasms was significantly lower than G3 (40.68 ± 45.65 cc) ones; moreover, DV of low risk neoplasms (6.98 ± 8.08 cc) was significantly lower than medium (21.7 ± 17.13 cc) and high risk (62.9 ± 51.12 cc) ones and DV of medium risk neoplasms was significantly lower than high risk ones. The intra-/inter-observer variability for DV measurement showed an excellent correlation for both cancers (ICC ≥ 0.86).Conclusions: DV is an accurate index for the assessment of G and risk classification of cervical/endometrial cancers with low intra-/inter-observer variability. [ABSTRACT FROM AUTHOR]

Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations. [ABSTRACT FROM AUTHOR]

In the extracellular space, the gonadotropin-releasing hormone (GnRH) is metabolized by the zinc metalloendopeptidase EC3.4.24.15 (EP24.15) to form the pentapeptide, GnRH-(1–5). GnRH-(1–5) diverges in function and mechanism of action from GnRH in the brain and periphery. GnRH-(1–5) acts on the orphan G protein-coupled receptor 101 (GPR101) to sequentially stimulate epidermal growth factor (EGF) release, phosphorylate the EGF receptor (EGFR), and facilitate cellular migration. These GnRH-(1–5) actions are dependent on matrix metallopeptidase (MMP) activity. Here, we demonstrated that these GnRH-(1–5) effects are dependent on increased MMP-9 enzymatic activity in the Ishikawa and ECC-1 cell lines. Furthermore, the effects of GnRH-(1–5) mediated by GPR101 and the subsequent increase in MMP-9 enzymatic activity lead to an increase in cellular invasion. These results suggest that GnRH-(1–5) and GPR101 regulation of MMP-9 may have physiological relevance in the metastatic potential of endometrial cancer cells. [ABSTRACT FROM AUTHOR]

Micronucleus ( MN) is an additional, small nucleus formed due to failure of incorporation of a fragment or the whole chromosome into the main daughter nuclei during cell division. MN scoring is a useful indicator of exposure to genotoxic agents and of malignancy. This study was conducted to know whether the MN score was significantly different in cervical cytology smears of patients with endometrial carcinoma, atypical and benign cells. Three groups of cervical smears were taken up for MN scoring: Group 'A' included benign endometrial cells, Group 'B', atypical glandular cells - endometrial and Group 'C', endometrial adenocarcinoma. Post hoc analysis of variance test was used to determine significant differences between the three groups. There were 30 cases in Group 'A', 31 cases in Group 'B' and 39 cases in Group 'C'. The mean MN score was 0.67 ± 0.711 in Group A, 1.74 ± 0.930 in Group B and 4.10 ± 2.500 in Group C. MN scores were significantly different between all three groups (p < 0.05). The MN score is significantly higher in cervical smears of patients with endometrial carcinoma; as compared to smears showing atypical and benign cells and that this finding may be useful for further research. [ABSTRACT FROM AUTHOR]

Objective We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer. Methods After pathology review, only endometrioid tumors with high neoplastic cellularity (≥ 70%) and high quality DNA for molecular analyses were included. MSI (microsatellite instability) typing was performed and the target sequence in exon 10 of ATR was evaluated by direct sequencing in all MSI-high tumors. Associations between ATR mutations and clinicopathologic variables were assessed using contingency table tests. Differences in overall survival (OS) and disease-free survival (DFS) were evaluated by univariate analyses and multivariable Cox proportional hazard models. Results A total of 475 eligible cases were identified. Of 368 MSI + cases, the sequence of interest could be successfully genotyped in 357 cases. ATR mutations were exclusively identified in 46 tumors with high level microsatellite instability (MSI +) (12.9%, p < 0.001) and were associated with higher tumor grade (p = 0.001). ATR mutations were not associated with OS (HR 1.16; 95% CI, 0.58–2.32; p = 0.68) or DFS (HR 0.61; 95% CI, 0.25–1.50; p = 0.28). Conclusion Truncating mutations in exon 10 of ATR occur exclusively in tumors with evidence of defective DNA mismatch repair. We were not able to confirm the prognostic value of these mutations in patients with endometrioid endometrial cancer. [ABSTRACT FROM AUTHOR]

Background Therapeutic options are limited for uterine serous carcinoma (USC). TP53 , PIK3CA , FBXW7 , and ERBB mutations, as well as HER2 and EGFR overexpression have been reported. We aim to evaluate patterns of molecular, genomic and protein changes in 628USC tumors. Methods 628 consecutive cases of USC submitted to Caris Life Sciences from Mar, 2011 to July, 2014 were reviewed. These were analyzed using the Illumina TruSeq Amplcon Cancer panel to search for sequenced variants in 47 genes commonly implicated in carcinomatosis. In situ hybridization and immunohistochemistry were also used to assess copy number and protein expression, respectively, of selected genes. Results 31 out of 47 genes of interest harbored mutations, including TP53 (76%), PIK3CA (29%), FBXW7 (12%) and KRAS (9.3%). BRCA1 and BRCA2 were mutated in 9.1% and 6.3%, respectively. ERCC1 and MGMT were absent in 81% and 46% of tumors analyzed, respectively, suggesting potential benefit from platinum and alkylating agents. While not traditionally considered hormone-dependent, our cohort showed high ERα (60%), PR (32%), and AR (27%) expression. HER2 overexpression was 10% via IHC, amplification was 17% via CISH/FISH and mutation was 2% via NGS. While low in PTEN mutation frequency (7%), 45% of USC showed PTEN loss on IHC, and 29% harbored PIK3A mutation, suggesting deregulation of P13K/AKT pathway in a subset of patients. 11% expressed PDL1 and 67% expressed PD1. Conclusions Our findings suggest hormonal receptors, as well as genes implicated in DNA repair, cell proliferation and cell cycle pathways are of interest in USC. [ABSTRACT FROM AUTHOR]