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Abnormal female reproductive tract microbiota are associated with gynecological disorders such as endometriosis or chronic endometritis and may affect reproductive outcomes. However, the differential diagnostic utility of the vaginal or the endometrial microbiome and the impact of important technical covariates such as the choice of hypervariable regions for 16 S rRNA sequencing remain to be characterized. The aim of this retrospective study was to compare vaginal and endometrial microbiomes in IVF patients diagnosed with implantation failure (IF) and/or recurrent pregnancy loss (RPL) and to investigate the overlap between established vaginal and endometrial microbiome classification schemes. An additional aim was to characterize to which extent the choice of V1-V2 or V2-V3 16 S rRNA sequencing schemes influences the characterization of genital microbiomes. We compared microbiome composition based on V1-V2 rRNA sequencing between matched vaginal smear and endometrial pipelle-obtained biopsy samples (n = 71); in a sub-group (n = 61), we carried out a comparison between V1-V2 and V2-V3 rRNA sequencing. Vaginal and endometrial microbiomes were found to be Lactobacillus-dominated in the majority of patients, with the most abundant Lactobacillus species typically shared between sample types of same patient. Endometrial microbiomes were found to be more diverse than vaginal microbiomes (average Shannon entropy = 1.89 v/s 0.75, p = 10−5) and bacterial species such as Corynebacterium sp., Staphylococcus sp., Prevotella sp. and Propionibacterium sp. were found to be enriched in the endometrial samples. The use of two widely used clinical classification schemes to detect microbiome dysbiosis in the reproductive tract often led to inconsistent results vaginal community state type (CST) IV, which is associated with bacterial vaginosis, was detected in 9.8% of patients; however, 31,0% of study participants had a non-Lactobacillus-dominated (NLD) endometrial microbiome associated with unfavorable reproductive outcomes. Results based on V2-V3 rRNA sequencing were generally consistent with V1-V2-based; differences were observed for a small number of species, e.g. Bifidobacterium sp., Propionibacterium sp. and Staphylococcus sp. and with respect to slightly increased detection rates of CST IV and NLD. Our study showed that endometrial microbiomes differ substantially from their vaginal counterparts, the application of a trans-cervical sampling method notwithstanding. Characterization of endometrial microbiomes may contribute to the improved detection of women with an unfavorable reproductive outcome prognosis in IVF patients.. [ABSTRACT FROM AUTHOR]

To investigate the effect of transcutaneous acupoint bioelectric stimulation on regulating the expression of inflammatory factors on endometrial repair after artificial abortion. Methods: 120 patients who underwent artificial abortion were divided into blank group (n=40, routine anti-infection treatment after operation), control group (n=40, bioelectric stimulation treatment on the basis of blank group) and observation group (n=40, transcutaneous acupoint bioelectric stimulation treatment on the basis of blank group). The endometrial thickness, vaginal bleeding volume, inflammatory factors [tumor necrosis factor-a (TNF-a), interleukin (IL)-8, IL-4, IL-10], menstrual recovery time, incidence of uterine curettage again and incidence of pelvic inflammatory disease were compared among three groups. Results: After treatment, the vaginal bleeding volume, TNF-a and IL-8 in observation group were lower than those in control group and blank group, and the endometrial thickness was greater than that in blank group and control group (P<0.05). And the levels of IL-4 and IL-10 were higher than those in control group and blank group (P<0.05). After treatment, the incidence of uterine curettage again and the incidence of pelvic inflammatory disease in observation group were lower than those in blank group and control group, and the time of menstruation recovery was shorter than that in blank group and control group (P<0.05). Conclusion: Patients after artificial abortion receiving transcutaneous acupoint bioelectric stimulation, which can promote endometrial repair and improve clinical symptoms by regulating the expression of inflammatory factors. [ABSTRACT FROM AUTHOR]

Background: PFASs, synthetic chemicals, can be encountered by humans through occupational or environmental exposure, and some reports suggest that they can disrupt endocrine and hormonal activities. In this comprehensive review and meta-analysis, we explored the connection between exposure to PFASs and the risks of breast and female genital cancers. Methods: We systematically reviewed the literature from IARC Monographs, ATSDR documents, and PubMed (as of January 2024) for cohort, case-control, and ecological studies on PFAS exposure and breast or female genital cancers. Four reviewers independently screened studies, and data extraction included study design, patient characteristics, and effect size measures. The quality of studies was assessed using the modified version of the Newcastle-Ottawa Scale (NOS). Forest plots of relative risks (RR) were constructed for breast and female genital cancer. Meta-analyses were conducted using random-effects models, stratified analyses, dose-response assessments, and publication bias evaluation. Results: The meta-analysis included 24 studies, comprising 10 cohort, 13 case-control, and one ecological study. The summary relative risk (RR) of breast cancer for PFOA exposure was 1.08 (95% CI = 0.97-1.20; n=21), and for PFOS was 1.00 (95% CI = 0.85-1.18; n=12). The RR for ovarian cancer and PFAS was 1.07 (95% CI = 1.04-1.09; n=12). The stratification by quality score, year of publication, and exposure source did not reveal any differences. However, analysis by geographical region (p=0.01) and study design (p=0.03) did show differences, particularly in terms of incidence. Stratified analyses of the dose-response relationship did not reveal a trend in the risk of breast cancer or female genital cancers, and no publication bias was found for either cancer type. No results were available for cervical and endometrial cancers. Conclusion: In summary, our results suggest an association between PFAS exposure and ovarian cancer and a possible effect on breast cancer incidence in some specific groups. However, bias and confounding cannot be excluded and prevent conclusions regarding causality. [ABSTRACT FROM AUTHOR]

Chlamydia abortus is a reported cause of infertility and endometritis in sheep, cattle, and pigs; however, the association between uterine disease and C. abortus is poorly understood in horses. Recently, a high prevalence of C. abortus in equine aborted chorioallantoises was reported in horses in western Canada. Based on this high prevalence, investigation into the effects of C. abortus on infertility and endometritis in western Canadian mares is prudent. We examined 98 formalin-fixed, paraffin-embedded endometrial biopsies from western Canada submitted between 2014 and 2022 using a Chlamydia -specific 16S rRNA PCR test; 40 samples tested positive for Chlamydia on PCR, and 28 were sequenced as C. abortus. The C. abortus –positive cases were primarily associated with a history of failure to conceive, early embryonic loss, or abortion. Our findings suggest that C. abortus may be a cause of conception failure and abortion in horses in western Canada. [ABSTRACT FROM AUTHOR]

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The uterine environment provides necessary conditions for the existence of endometrial microbiota, which in turn plays an important role in maintaining the homeostasis of the uterine environment. The endometrial microbiome is highly susceptible to external factors such as age, hormones, menstrual, pregnancy, etc. When the microbiota is imbalanced, it will further promote the occurrence of uterine diseases such as endometritis and endometrial cancer. Regulating the microbiome of the endometrium is of positive significance for promoting uterine health. Among them, antibiotics, probiotics, prebiotics, and microbial transplantation may be important pathways for regulating endometrial microbiota in the future. However, there is currently no unified plan for evaluating the endometrial microbiota. In addition, due to the small sample size, it is easy to be contaminated by exogenous bacterial DNA, which poses great challenges for studying the mechanism of microbial community regulating uterine health. Therefore, there are still many areas worth exploring for the future of endometrial microbiome. [ABSTRACT FROM AUTHOR]

Objective: The effects of hormonal therapy, estrogen-based hormone replacement therapy (HRT), and anti-tumor hormone therapy, such as tamoxifen, on the physiological uptake of the endometrium on 2-deoxy-2[18F]fluoro-d-glucose ([18F]F-FDG) positron emission tomography (PET) in postmenopausal women have not been determined. We explored the effect of hormone therapy, particularly HRT, on physiological uptake in the endometrium of postmenopausal women. Materials and methods: Postmenopausal women receiving hormone therapy who underwent cancer screening using PET/computed tomography (CT) between June 2016 and April 2023 were included in the hormone therapy group (n = 21). Postmenopausal women with no history of hormone therapy were included in the control group (n = 49). First, the physiological endometrial uptake at menopausal age and at least 1 year thereafter was compared quantitatively (SUVmax) and qualitatively (4-point scale) in the control group, to assess when the endometrium ceased to show significant physiological [18F]F-FDG uptake after menopause. Endometrial uptake was compared between the hormone therapy and control groups. The association between HRT duration (months) and endometrial uptake (SUVmax) was evaluated. Endometrial thickness, measured using transvaginal ultrasonography, was also compared between the two groups. Results: Endometrial uptake was significantly reduced both qualitatively and quantitatively (P < 0.05) at least 1 year after menopause in control patients, by which time most women (89.8%) no longer had significant endometrial uptake. The hormone therapy group (n = 21) showed higher FDG uptake in the endometrium compared to the control group (median SUVmax: 2.3 vs 1.9, P = 0.0011), as well as a higher visual score (P < 0.0001). HRT duration did not correlate with endometrial uptake (P = 0.097). Endometrial thickness in the hormone therapy group was significantly thicker than in the control group (median: 3.9 mm vs 1.8 mm, P = 0.002). Conclusion: Hormone therapy may affect physiological uptake in the endometrium in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Ewing sarcoma is an EWSR1-rearranged aggressive malignancy that occurs commonly in bone and has small round blue cell morphology. A diagnostic challenge is presented in the cases of extraskeletal Ewing sarcoma involving solid organs, such as the uterus. Case report and brief literature review: We present the case of a 54-year-old female with a large pelvic mass connected to the uterine cornua and retroperitoneal soft tissue. Upon surgical debulking, the mass was characterized by infiltrative tumor cells with high nuclei-to-cytoplasmic ratio invading from the serosal surface into the myometrium. The initial diagnostic work-up was muddied by radiographic suggestion of uterine origin, histologic identification of uterine involvement and diffuse positivity for Cyclin D1, KIT and CD99, which raised the diagnostic possibility of high-grade endometrial stromal sarcoma. However, molecular testing that revealed EWSR1::FLI fusion, indicative of Ewing sarcoma. She was thus referred from the gynecologic oncology service to the soft tissue sarcoma service for adjuvant chemotherapy of vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide (VDC/IE). We performed a literature review highlighting immunohistochemical and molecular features along with treatment and outcomes in case series of YWHAE-rearranged high-grade endometrial stromal sarcomas and Ewing sarcoma with uterine and/or retroperitoneal involvement. Conclusion: This case and accompanying literature review highlight the benefit of molecular testing in the context of round cell tumors involving the uterus and the importance of distinguishing high-grade uterine stromal sarcomas from sarcomas of soft tissue origin, as they have different treatment strategies.

The endometrial microbiome is a rapidly advancing field of research, particularly in obstetrics and gynecology, as it has been found to be linked with obstetric complications and potential impacts on fertility. The diversity of microorganisms presents in the endometrium, along with their metabolites, can influence reproductive outcomes by modulating the local immune environment of the uterus. However, a major challenge in advancing our understanding of the endometrial microbiota lies in the heterogeneity of available studies, which vary in terms of patient selection, control groups, collection methods and analysis methodologies. In this study, we propose a detailed pipeline for endometrial microbiome analysis, based on the most comprehensive prospective of 64 studies that have investigated the endometrial microbiome up to the present. Additionally, our review suggests that a dominance of Lactobacilli in the endometrium may be associated with improved reproductive prognosis, including higher implantation rates and lower miscarriage rates. By establishing a standardized pipeline, we aim to facilitate future research, enabling better comparison and correlation of bacterial communities with the health status of patients, including fertility-related issues. [ABSTRACT FROM AUTHOR]

Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk. To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA). We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA. We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients – affected genes included GLI1 , PIK3R1 , FOXP1 , FANCD2 , INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses. Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy. • High-grade serous carcinoma (HGSC) carries a high mortality. • Goal: Expand upon methods for early identification of potential candidates for risk-reducing salpingo-oophorectomy (RRSO). • We performed comprehensive NGS on tumor and normal tissues. • We identified rare germline variants in patients with concurrent endometrial and tubo-ovarian cancers. • Comprehensive genetic profiling may aid in early identification of patient relatives who may benefit from RRSO. [ABSTRACT FROM AUTHOR]

Simple Summary: In the past few years, the endometrial cancer field has been revolutionized, following the integration of molecular classification into clinical practice. Endometrial carcinoma is currently molecularly categorized into four main subgroups: POLE-mutated, mismatch repair-deficient, p53-mutated, and no specific molecular profile. The POLE-mutated subgroup is characterized by an excellent prognosis notwithstanding bad conventional prognostic factors, including high-grade and TP53 mutations. On the other hand, the p53-mutated subgroup demonstrates the worst outcome. However, the remaining subgroups are more prevalent and display variable clinical outcomes. In this review, we describe the evolution of the endometrial carcinoma classification, its strengths and limitations, clinical implications, and foreseen perspectives. Endometrial carcinoma (EC) is the most frequent gynecological cancer, with an increasing incidence and mortality in recent times. The last decade has represented a true revolution with the development of the integrated histo-molecular classification of EC, which allows for the stratification of patients with morphologically indistinguishable disease into groups with different prognoses. Particularly, the POLE-mutated subgroup exhibits outstanding survival. Nevertheless, the indiscriminate application of molecular classification appears premature. Its prognostic significance has been proven mainly in endometrioid EC, the most common histotype, but it has yet to be convincingly confirmed in the other minor histotypes, which indeed account for a relevant proportion of EC mortality. Moreover, its daily use both requires a mindful pathologist who is able to correctly evaluate and unambiguously report immunohistochemical staining used as a surrogated diagnostic tool and is hampered by the unavailability of POLE mutation analysis. Further molecular characterization of ECs is needed to allow for the identification of better-tailored therapies in different settings, as well as the safe avoidance of surgery for fertility preservation. Hopefully, the numerous ongoing clinical trials in the adjuvant and metastatic settings of EC will likely produce evidence to refine the histo-molecular classification and therapeutic guidelines. Our review aims to retrace the origin and evolution of the molecular classification for EC, reveal its strengths and limitations, show clinical relevance, and uncover the desired future developments. [ABSTRACT FROM AUTHOR]

This case report describes a 45-year-old woman presenting with abnormal uterine bleeding and a cervical mass. Imaging and biopsy revealed low-grade endometrial stromal sarcoma (LGESS), emphasizing the importance of comprehensive evaluation for uterine masses. The report underscores the role of MRI and pathology in diagnosis, with immunohistochemical analysis helping confirmation. A multidisciplinary approach and vigilant follow-up are crucial for optimal management. The rarity of LGESS and its challenging diagnosis highlight the need for continued research to improve diagnostic and therapeutic strategies. Surgical intervention remains primary, but the optimal management approach is debated. This report indicates the necessity of a comprehensive approach to uterine mass evaluation and ongoing research for enhanced patient care.

Introduction: Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal fibroids are common etiologies of post menopausal bleeding. The most common cause of postmenopausal bleeding is endometrial atrophy, comprises of 60-80%, while endometrial hyperplasia and endometrial cancer contribute to only 11% of Post menopausal bleeding. The aim of study is to analyses histomorphological pattern of endometrium in patients presenting with post-menopausal bleeding in Jharkhand. Materials and Methods: 103 postmenopausal women presenting to tertiary center of Jharkhand in 2020-22 with bleeding were subjected to endometrial curettage for histopathology. Analysis is based on morphological criteria to assess endometrium. Endometrial histology is of four categories: Proliferative, Secretory, premalignant and carcinoma. Results: The highest incidence of postmenopausal bleeding was noticed in age group of < 60 years and incidence of malignancy was higher after 57 years of age. The majority of patients had parity between 1 and 3 (78.6%). Malignant & premalignant lesions comprises about 22.3% among that 77.7% were due to benign causes. Among the benign causes of postmenopausal bleeding, proliferative endometrium was the commonest finding. Types of hyperplasia encountered were simple hyperplasia without atypia (6.8%), Complex hyperplasia without atypia (3.9%),Complex hyperplasia with atypia (4.8%) and Simple hyperplasia with atypia (4.8%). 21.4% of cases of postmenopausal bleeding were associated with atrophic endometrium. Secretory endometrium seen in 17.5% of women. Endometrial carcinoma accounted for 12.6% of cases of postmenopausal bleeding. Out of these 69.2% were of endometroid type of endometrial carcinoma, 15.3% were of papillary serous carcinoma and 15.3% had clear cell carcinoma. The mean age of patients with endometrium carcinoma was 62.3 years. All cases of endometrial carcinoma were associated with 1 or more risk factor like diabetes/hypertension/Nulligravida. Conclusion: Proliferative Endometrium was a major cause of postmenopausal bleeding. Among the malignant causes, endometrial adenocarcinoma of endometroid type was most frequent with a lower mean age at presentation than other high grade cancers like papillary serous carcinoma & clear cell carcinoma.

Background: Atypical glandular cells (AGCs) diagnosis on Pap (Papanicolaou) smears are uncommon and may represent various benign and malignant lesions. Objective: This study aims to report the incidence of AGC on Pap smear, to study the relationship of AGC with malignancy, and to determine cytomorphological features that help in predicting malignancy. Materials and Methods: Retrospective analytical study conducted in the Department of Oncopathology at Tertiary Cancer and Research Institute. In this retrospective study, we included cases diagnosed with AGC between July 2017 to July 2022. All slides were reviewed and subclassified according to the Bethesda 2014 classification system (TBS). The predetermined cytomorphological features observed in the smears were recorded. The follow-up histopathological diagnoses of the cases were retrieved. The significant cytomorphological and clinicopathological findings for malignancy were determined. Results: Pearson χ2 test with SPSS software version 22 to compare cytologic features of cases with benign and malignant follow-up. The significant cytomorphological features observed in neoplastic cases were cells in 3-dimensional clusters, nuclear overlapping, reniform nucleus, irregular nuclear membrane, increased nuclear size, single macronucleoli, engulfed neutrophils, and prominently vacuolated cytoplasm. Conclusions: The diagnosis of AGC on cytology is associated with clinically significant lesions, and cytomorphologic parameters can be used to predict the benign and malignant outcome.

Introduction: Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal fibroids are common etiologies of post menopausal bleeding. The most common cause of postmenopausal bleeding is endometrial atrophy, comprises of 60-80%, while endometrial hyperplasia and endometrial cancer contribute to only 11% of Post menopausal bleeding. The aim of study is to analyses histomorphological pattern of endometrium in patients presenting with post-menopausal bleeding in Jharkhand. Materials and Methods: 103 postmenopausal women presenting to tertiary center of Jharkhand in 2020-22 with bleeding were subjected to endometrial curettage for histopathology. Analysis is based on morphological criteria to assess endometrium. Endometrial histology is of four categories: Proliferative, Secretory, premalignant and carcinoma. Results: The highest incidence of postmenopausal bleeding was noticed in age group of < 60 years and incidence of malignancy was higher after 57 years of age. The majority of patients had parity between 1 and 3 (78.6%). Malignant & premalignant lesions comprises about 22.3% among that 77.7% were due to benign causes. Among the benign causes of postmenopausal bleeding, proliferative endometrium was the commonest finding. Types of hyperplasia encountered were simple hyperplasia without atypia (6.8%), Complex hyperplasia without atypia (3.9%),Complex hyperplasia with atypia (4.8%) and Simple hyperplasia with atypia (4.8%). 21.4% of cases of postmenopausal bleeding were associated with atrophic endometrium. Secretory endometrium seen in 17.5% of women. Endometrial carcinoma accounted for 12.6% of cases of postmenopausal bleeding. Out of these 69.2% were of endometroid type of endometrial carcinoma, 15.3% were of papillary serous carcinoma and 15.3% had clear cell carcinoma. The mean age of patients with endometrium carcinoma was 62.3 years. All cases of endometrial carcinoma were associated with 1 or more risk factor like diabetes/hypertension/Nulligravida. Conclusion: Proliferative Endometrium was a major cause of postmenopausal bleeding. Among the malignant causes, endometrial adenocarcinoma of endometroid type was most frequent with a lower mean age at presentation than other high grade cancers like papillary serous carcinoma & clear cell carcinoma. [ABSTRACT FROM AUTHOR]

Background & Objective: Endometrial Carcinoma (EC) is the most common gynecological cancer with a global incidence of 23.2 per 1 lakh population. Histological subclassification of EC is extremely crucial for the diagnosis, proper management strategies, and prognosis. This study was conducted in a tertiary care institute to analyze the expression pattern of a minimum panel of 4 markers (ER, p53, CEA, Napsin A) with emphasis on their utility in the routine histological subtyping, aberrant expression, and correlation with various clinicopathological parameters. Methods: A time-bound cross-sectional observational and analytical study was conducted, which includes cases diagnosed in our laboratory from January 2016 to April 2021. Results: Sixty cases diagnosed as EC during the study period formed the sample cases. The ER was expressed in 85% (53/60) of cases in the current study. Among them, 94% (50/53) were endometrioid endometrial carcinomas (EECs). A negative correlation was found between ER intensity and age (r= -1.48). Of 60 EC cases, 10 (16%) cases expressed p53. The tumors positive for p53 with higher intensity were negative for ER and vice versa. The expression pattern of ER and p53 was statistically significant (P=-0.021). On IHC, 84.6% (11/13) of CEA-positive cases expressed both ER and CEA, suggesting mucinous differentiation. Napsin A was expressed in two cases of EEC, FIGO grade I, and one case of serous carcinoma. Conclusion: An inverse association was found between ER and p53 expression. The CEA is valuable in identifying EEC with mucinous differentiation. [ABSTRACT FROM AUTHOR]

Purpose: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. Methods: We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. Results: We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. Conclusions: The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription. [ABSTRACT FROM AUTHOR]

Background: Atypical glandular cells (AGCs) diagnosis on Pap (Papanicolaou) smears are uncommon and may represent various benign and malignant lesions. Objective: This study aims to report the incidence ofAGC on Pap smear, to study the relationship ofAGC with malignancy, and to determine cytomorphological features that help in predicting malignancy. Materials and Methods: Retrospective analytical study conducted in the Department of Oncopathology at Tertiary Cancer and Research Institute. In this retrospective study, we included cases diagnosed with AGC between July 2017 to July 2022. All slides were reviewed and subclassified according to the Bethesda 2014 classification system (TBS). The predetermined cytomorphological features observed in the smears were recorded. The follow-up histopathological diagnoses of the cases were retrieved. The significant cytomorphological and clinicopathological findings for malignancy were determined. Results: Pearson χ² test with SPSS software version 22 to compare cytologic features of cases with benign and malignant follow-up. The significant cytomorphological features observed in neoplastic cases were cells in 3-dimensional clusters, nuclear overlapping, reniform nucleus, irregular nuclear membrane, increased nuclear size, single macronucleoli, engulfed neutrophils, and prominently vacuolated cytoplasm. Conclusions: The diagnosis of AGC on cytology is associated with clinically significant lesions, and cytomorphologic parameters can be used to predict the benign and malignant outcome. [ABSTRACT FROM AUTHOR]

Background: Conservative management of atypical endometrial hyperplasia (AEH) or endometrial cancer (EMCA) often relies on the treatment of synthetic progestins, which show varied success and response rates. We evaluate the correlation between steroid receptor expression and response to progestin therapy in patients with AEH and EMCA. Methods: Retrospective cohort study collected data for patients with AEH or EMCA who had an endometrial sample after receiving conservative therapy utilizing either Megestrol acetate or Levonorgestrel Intrauterine device (IUD). Immunohistochemistry (IHC) was performed on pre- and post- treatment biopsy samples to assess androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) expression. IHC scores (1–12) were calculated based on staining intensity and percentage of positive cells. Results and analysis: We identified 15 patients with AEH and EMCA between 2015 and 2023 with the majority of African American ethnicity (53 %). Fourteen patients (93 %) received Megestrol acetate, and 1 patient received Levonorgestrel IUD alone. Three patients ultimately underwent hysterectomy. Seven (46.6 %) endometrial samples had strong positivity for AR, PR and ER expression on pre-treatment biopsies, and only 3 (20 %) of them maintained strong positivity for the 3 receptors in the post-treatment. Patients who successfully responded to the treatment demonstrated a significantly greater decrease in IHC scores after the treatment compared to those who did not respond (p = 0.009). Conclusion: Steroid receptor expression could be used as a possible biomarker for response to progestin therapy in patients undergoing conservative management for AEH and EMCA.

Introduction: Endometrial hyperplasia affects both premenopausal and postmenopausal women and is a pathological condition that ranges from mild, reversible glandular proliferations to direct precursors of cancer. B-cell Lymphoma 2 (Bcl-2), an antiapoptotic gene involved in the regulation of apoptosis, and Ki-67, a proliferation marker, serve as indicators for cell proliferation from endometrial hyperplasia to endometrial carcinoma. Aim: To examine the expression of Bcl-2 and Ki-67 in endometrial hyperplasia and disordered endometrium. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at MVJ Medical College and Research Hospital, located in Hoskote, Karnataka, India, over a period of two years, from September 2020 to September 2022. All endometrial samples and hysterectomy specimens were included. Immunohistochemical staining was performed using Bcl-2 and Ki-67 in disordered proliferative endometrium and endometrial hyperplasia, and the staining and intensity were graded. Statistical analysis was performed, with qualitative variables presented as percentages and quantitative variables presented as Mean±Standard Deviation (SD). A p-value

Simple Summary: There is a lack of understanding as to whether the bacteria isolated from swabs of the surface of the lining of broodmares' uteri (endometrial swabs) are present due to infection or contamination, or whether they are, in fact, part of the normal flora. This study aimed to understand this further by investigating endometrial swabs taken from a population of Thoroughbred broodmares and submitted to a laboratory in the UK between 2014 and 2020; by describing bacterial prevalence (the estimated percentage of swabs from which bacteria are isolated); and by evaluating whether bacterial prevalence changed over time or between mares of different ages and with differing amounts of inflammation of the uterine lining. Over the 7-year period, 18,996 endometrial swabs were submitted from 6050 mares on 290 farms. The overall prevalence of bacteria was 35.5%. Beta-hemolytic Streptococcus (17.9%) and E. coli (10.3%) were the most prevalent types of bacteria. The prevalence of bacteria changed over time (between different years in which mares were sampled) and was also impacted by the mare age and by whether there was inflammation of the uterine lining at the time of sampling. Results from this study provide up-to-date prevalence estimates and suggest that the interpretation of Thoroughbred endometrial swab findings is complicated. Determining whether endometrial microbial isolates are pathogens, contaminants, or even part of the "normal" microbiome is extremely complex, particularly given the absence of "gold standard" tests for endometritis. Population-level benchmarking and temporal monitoring can provide novel insights and a wider context to improve understanding. This study aimed to (i) estimate the prevalence of endometrial isolates from swabs of Thoroughbred broodmares in Newmarket, UK between 2014 and 2020; and (ii) evaluate the effects of year, mare age, and cytology findings on isolate prevalence. Generalised linear mixed models with a logit link, both null models and models using year of sampling, mare age, or cytology findings as predictors, were fitted to estimate isolate prevalence. Over the 7-year period, data were available from 18,996 endometrial-swab samples from 6050 mares on 290 premises. The overall isolate prevalence was 35.5% (95% confidence interval (CI) 33.0–37.9), and this varied significantly between years. The most prevalent isolates were β-hemolytic Streptococcus (17.9; 95% CI: 17–19) and E. coli (10.3%; 95% CI: 9.0–11.6). Isolate prevalence increased with mare age except for E. coli isolates, and with increasing category of cytology findings except for α-hemolytic Streptococcus isolates. The results provide novel estimates of isolate prevalence and highlight knowledge gaps around potential complexities in the interpretation of findings. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, GnRH2 and GnRHR2 genes are present, but coding errors in the GnRHR2 gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues have potent anti-proliferative, pro-apoptotic, and/or antimetastatic effects on various reproductive cancers, including endometrial, breast, placental, ovarian, and prostate. Thus, GnRH2 is an emerging target to treat human reproductive cancers. [ABSTRACT FROM AUTHOR]

Background: Endometrial stromal tumors (ESTs) are rare subset of mesenchymal uterine neoplasms. There are heterogeneous morphological, immunohistochemical, and genetic features. Approximately 50% of ESTs occur in perimenopausal women. In 2020, WHO sub-categorized ESTs into four groups: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS), and undifferentiated uterine sarcoma (UUS). Objective: To review the morphological spectrum of endometrial stromal tumors. Method: This retrospective study reviewed the histomorphological features of 15 endometrial stromal tumors with respect to atypia, necrosis, mitosis, collagen bands, whorling around vessels, myometrial invasion, and inflammatory cells. Immunohistochemistry markers (CD10, SMA, and ER) along with special stains (Masson's trichrome, toluidine blue) were also studied. Results: The age of the patients ranged from 32 to 60 years. Three patients were postmenopausal. The most common presenting symptom was vaginal bleeding. Five patients were operated with a clinical diagnosis of uterine fibroid. One patient presented with prolapse with no other complaint. All the 15 patients had total abdominal hysterectomy and salpingo-oophorectomy. One case showed necrosis, eight cases showed collagen bands, all the 15 cases showed whorling around vessels, one case showed vascular emboli, and seven cases showed inflammatory cells. In low-grade cases, one case showed focal atypia and one case showed focal coagulative necrosis indicating infarction. Thirteen cases were LGESS, and one case of ESN and HGESS. All cases were positive for ER and CD10. Conclusion: Endometrial stromal tumors demonstrate extensive permeation of the myometrium as irregular islands with frequent vascular invasion, whorling around vessels, collagen bands, and inflammatory cells. All these features should be observed thoroughly on microscopy by pathologists to clearly differentiate the low-grade and high-grade endometrial stromal tumors, and to understand the overlapping gray areas morphologically as it affects the prognosis of the patient. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the positive predictive value (PPV) of an endometrial cancer case finding algorithm using International Classification of Disease 10th revision Clinical Modification (ICD‐10‐CM) diagnosis codes from US insurance claims for implementation in a planned post‐marketing safety study. Two algorithm variants were evaluated. Methods: Provisional incident endometrial cancer cases were identified from 2016 through 2020 among women aged ≥50 years. One algorithm variant used diagnosis codes for malignant neoplasms of uterine sites (C54.x), excluding C54.2 (malignant neoplasm of myometrium); the other used only C54.1 (malignant neoplasm of endometrium). A random sample of medical records of recent incident provisional cases (2018–2020) was requested for adjudication. Confirmed cases showed biopsy evidence of endometrial cancer, documentation of cancer staging, or hysterectomy following diagnosis. We estimated the PPV of the variants with 95% confidence intervals (CI) excluding cases that had insufficient information. Results: Of 294 provisional cases adjudicated, 85% were from outpatient settings (n = 249). Mean age at diagnosis was 69.3 years. Among the 294 adjudicated cases (identified with the broader algorithm variant), the same 223 were confirmed endometrial cancer cases by both algorithm variants. The PPV (95% CI) for the broader algorithm variant was 84.2% (79.2% and 88.3%), and for the variant using only C54.1 was 85.8% (80.9% and 89.8%). Conclusion: We developed and validated an algorithm using ICD‐10‐CM diagnosis codes to identify endometrial cancer cases in health insurance claims with a sufficiently high PPV to use in a planned post‐marketing safety study. [ABSTRACT FROM AUTHOR]

Background: Abnormal uterine bleeding (AUB) refers to irregularities in menstrual cycle involving frequency, regulatory, duration and volume of flow outside of pregnancy. AUB refers to any nonphysiologic uterine bleeding.[1] It affects great majority of women and is one of the most common problems in their life, most commonly occurring at menarche and peri-menopausal age. It is one of the most common indications for performing endometrial biopsies and curettage. A normal menstrual cycle has a frequency of 24–38 days and lasts 2-7 days with 5–80 ml of blood loss. Variations in any of these parameters constitute abnormal uterine bleeding. Aim: To study the morphology of endometrial lesions in cases presenting with AUB at PCMS hospital {BHOPAL}. Methods: The study was observational, analytical, retrospective and prospective that was carried out for period from Feb 2022 to June 2023 in department of pathology; at Peoples medical college of medical science and research Centre, Bhopal {MP}. Total 118 patients who were clinically diagnosed as AUB were studied. The samples received were endometrial biopsies, endometrial curettage, and hysterectomy specimens for study. Results: In cases of endometrial polyps, endometrium showed no other abnormality. Chronic endometritis was seen in 2 cases {1.6%} 3 cases of endometrial hyperplasia were seen in study. 2 cases {1.6 %} of non-atypical hyperplasia and 1 case {0.8%} of atypical hyperplasia was observed in this study. 1 case {0.8%} of endometrial carcinoma was found in this study. Maximum numbers of patients {69.4%} were found in perimenopausal age group (40-49 years). 19 patients {16.2%} were in reproductive age group (< 40 years) 17 patients {14.4%} were in post-menopausal age group (>49years) Conclusion: Endometrial biopsy is important investigation in diagnosis of cases of AUB. Findings in endometrial biopsy in AUB cases show wide range of histopathological finding, ranging from normal appearing endometrium to endometrial carcinoma which can be diagnosed on endometrial biopsy for its proper management. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, GnRH2 and GnRHR2 genes are present, but coding errors in the GnRHR2 gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues have potent anti-proliferative, pro-apoptotic, and/or anti-metastatic effects on various reproductive cancers, including endometrial, breast, placental, ovarian, and prostate. Thus, GnRH2 is an emerging target to treat human reproductive cancers.

ObjectiveLynch syndrome is the most common cause of inherited endometrial cancer, attributable to germline pathogenic variants (PV) in mismatch repair (MMR) genes. Tumor microsatellite instability (MSI-high) and MMR IHC abnormalities are characteristics of Lynch syndrome. Double somatic MMR gene PV also cause MSI-high endometrial cancers. The aim of this study was to determine the relative frequency of Lynch syndrome and double somatic MMR PV.Methods341 endometrial cancer patients enrolled in the Ohio Colorectal Cancer Prevention Initiative at The Ohio State University Comprehensive Cancer Center from 1/1/13-12/31/16. All tumors underwent immunohistochemical (IHC) staining for the four MMR proteins, MSI testing, and MLH1 methylation testing if the tumor was MMR-deficient (dMMR). Germline genetic testing for Lynch syndrome was undertaken for all cases with dMMR tumors lacking MLH1 methylation. Tumor sequencing followed if a germline MMR gene PV was not identified.ResultsTwenty-seven percent (91/341) of tumors were either MSI-high or had abnormal IHC indicating dMMR. As expected, most dMMR tumors had MLH1 methylation; (69, 75.8% of the dMMR cases; 20.2% of total). Among the 22 (6.5%) cases with dMMR not explained by methylation, 10 (2.9% of total) were found to have Lynch syndrome (6 MSH6, 3 MSH2, 1 PMS2). Double somatic MMR PV accounted for the remaining 12 dMMR cases (3.5% of total).ConclusionsSince double somatic MMR gene PV are as common as Lynch syndrome among endometrial cancer patients, paired tumor and germline testing for patients with non-methylated dMMR tumor may be the most efficient approach for LS screening.

Melanocytic metastasis to gynecologic organs is rare with most metastases to the ovaries. Metastases to the uterus, or in this case report, a uterine polyp, is exceedingly rare with only 17 cases reported in the literature. Post-menopausal bleeding is the most common presentation of metastatic melanoma in the endometrium, followed by uterine bleeding or abnormal postnatal bleeding in the premenopausal population. We present an 81-year-old woman with metastatic melanoma confined to an endometrial polyp leading to the diagnosis of widespread dissemination of the patient's acral melanoma resected 6 years prior. Although rare, metastatic melanoma should be considered as a cause for abnormal bleeding, especially in the post-menopausal patient with a history of melanoma.

Objectives Our aim was to explore the performance of TRPS1 as an immunohistochemical diagnostic marker; find the optimal conditions for its use in breast carcinomas, especially triple-negative breast cancers (TNBCs); and compare its results in carcinomas of a select few organ sites, with an emphasis on gynecologic tumors. Methods Tissue microarrays from breast carcinomas (n = 197), endometrial adenocarcinomas (n = 69), ovarian tumors (n = 250), vulvar squamous cell carcinomas (n = 97), pancreatic ductal adenocarcinomas (n = 20), and gastric adenocarcinomas (n = 12) were stained with TRPS1 using 2 different conditions (protocol 1: high pH; protocol 2: low pH). Breast carcinomas consisted of hormone receptor (HR)–positive/ERBB2 (formerly HER2 or HER2/neu)–negative (n = 53) samples, HR-positive/ERBB2-positive (n = 6) samples, and TNBCs (n = 138). Results Comparing TRPS1 results in breast carcinomas vs tumors from other organ sites, the sensitivity of TRPS1 was 91% and 87%, respectively, while the specificity was 66% and 74% for protocol 1 and 2, respectively. For TNBCs vs gynecologic tumors, the sensitivity of TRPS1 was 89% and 85%, respectively, while the specificity was 65% and 73%, respectively. Conclusions TRPS1 stains approximately 90% of breast carcinomas but also up to 71% of endometrial carcinomas, albeit with a weaker median expression. Our data show that although TRPS1 is a highly sensitive marker for TNBCs, it is not as highly specific as previously reported. [ABSTRACT FROM AUTHOR]

Background: Abnormal uterine bleeding (AUB) that is any irregularity in menstrual cycles causes women to refer to clinics. This study aimed to compare the efficacy, safety, and complications of endometrial ablation by the thermal balloon (Cavaterm) method with the hysteroscopy loop resection method in the treatment of AUB.Materials and Methods: The present study is an open-label, randomized clinical trial that was performed in the two hospitals, Shahid Akbarabadi and Hazrat Rasoul Akram, of Tehran, Iran, from December 2019 to October 2020. Patients were randomly allocated to the two groups of interventions by a simple randomization method. The proportion of amenorrhea (as primary outcome) and consequent hysterectomy and patient satisfaction (as secondary outcomes) was assessed using the Chi-square test and independent t test.Results: There was no significant difference between the two groups in the baseline characteristics. The percentage of intervention failure was statistically higher in the hysteroscopy group (24%) in comparison with the Cavaterm group [8.2%, P=0.03, relative risk (RR)=1.63, 95% confidence interval (CI): 1.13-2.36]. Mean ± standard deviation of satisfaction based on the Likert score in the Cavaterm group and hysteroscopy group were 4.3 ± 1.21 and 3.7 ± 1.56, respectively, that showed a significant difference (P=0.04). Assessing the procedural complications, the rate of spotting, bloody discharge, and malodor discharge was significantly higher in the Cavaterm group. In contrast, postoperative dysmenorrhea is more common in the hysteroscopy group.Conclusion: Cavaterm ablation is accompanied by a higher success rate of amenorrhea and patients’ satisfaction than hysteroscopy ablation (registration number: IRCT20220210053986N1).

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. [ABSTRACT FROM AUTHOR]

Endometrial tuberculosis (TB) is an uncommon manifestation of disseminated TB. Rhupus is the coexistence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We describe a case of endometrial TB in rhupus patient an immunosuppressed. Contribution: We describe an uncommon presentation of disseminated TB, endometrial TB, in a rare rheumatic disease, rhupus. A high index of suspicion for TB is imperative in immunocompromised patients presenting with chronic urogenital symptoms especially in an endemic area.

To provide a systematic review of the applications of 3D printing in gynecological brachytherapy. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Purpose: To compare Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in patients with endometrial cancer receiving adjuvant pelvic radiation therapy with proton beam therapy (PT) versus intensity-modulated radiation therapy (IMRT). Materials and Methods: Patients with uterine cancer treated with curative intent who received either adjuvant PT or IMRT between 2014 and 2020 were identified. Patients were enrolled into a prospective registry using a gynecologic-specific subset of PRO-CTCAE designed to assess symptom impact on daily living. Questions included gastrointestinal (GI) symptoms of diarrhea, flatulence, bowel incontinence, and constipation in addition to other pertinent gynecologic, urinary, and other general symptoms. Symptom-based questions were on a 0- to 4-point scale, with grade 3+ symptoms occurring frequently or almost always. Patient-reported toxicity was analyzed at baseline, end of treatment (EOT), and at 3, 6, 9, and 12 months after treatment. Unequal variance t tests were used to determine if treatment type was a significant factor in baseline-adjusted PRO-CTCAE. Results: Sixty-seven patients met inclusion criteria. Twenty-two received PT and 45 patients received IMRT. Brachytherapy boost was delivered in 73% of patients. Median external beam dose was 45 Gy for both PT and IMRT (range, 45–58.8 Gy). When comparing PRO-CTCAE, PT was associated with less diarrhea at EOT (P = .01) and at 12 months (P = .24) than IMRT. Loss of bowel control at 12 months was more common in patients receiving IMRT (P = .15). Any patient reporting grade 3+ GI toxicity was noted more frequently with IMRT (31% versus 9%, P = .09). Discussion: Adjuvant PT is a promising treatment for patients with uterine cancer and may reduce patient-reported GI toxicity as compared with IMRT.

Abstract Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. Results Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. Conclusions These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

Objective: To investigate the therapeutic effect of chorionic gonadotropin on recurrent abortion in rats, and to provide a theoretical basis for optimizing the treatment of recurrent abortion in clinical practice. Methods: Forty unmated SPF female rats were randomly divided into control group (group A), model group (group B), conventional treatment group (group C) and chorionic gonadotropin treatment group (group D), with 10 rats in each group. The intervention began after the female was pregnant. Rats in group A were only given normal saline throughout the day. Rats in group B were given normal saline in the morning, rats in group C were given dydrogesterone in the morning, rats in group D were given chorionic gonadotropin injection in the morning, and rats in groups B, C, and D were given hydroxyurea solution in the afternoon. On the tenth day of gestation, rats in each group were given mifepristone. The embryonic absorption rate, inflammatory factor level, immune factor level, estrogen receptor expression level and endometrial injury degree of each group were compared. Results: After the intervention, the embryo absorption rate was increased in each group compared with group A, and lower in group C and D rats compared with group B rats, and group D rats were lower than group C rats; Compared with group A, the levels of IL-17, IL-17/TGF-β, the proportion of Th17 cells and Th17/Treg in each group were increased, and the levels of TGF-β and the proportion of Treg cells were decreased. At the same time, the levels of IL-17, IL-17/TGF-β, Th17 cell ratio and Th17/Treg in groups C and D were lower than those in group B, and the levels of TGF-β and Treg cell ratio in group D were higher than those in group B, and those in group D were higher than those in group C. After intervention, compared with group A, the endometrial thickness of rats in each group decreased and the proportion of fibrosis area increased. Compared with group B, the endometrial thickness of rats in groups C and D increased, and the proportion of endometrial fibrosis in group D was higher than that in group C, and the proportion of endometrial fibrosis in group D was lower than that in group B, and the proportion of endometrial fibrosis in group D was lower than that in group C. Compared with group A, the m RNA expression levels of ER, PR and PRLR of rats in each group were significantly decreased; compared with group B, the m RNA expression levels of ER, PR and PRLR of rats in groups C and D were increased, and group D was higher than group C, the differences were statistically significant (P＜0.05) . Conclusion: Chorionic gonadotrophin may improve the expression of sex hormone receptors by regulating the level of inflammatory factors and immune microenvironment, and then repair endometrial injury, reduce embryo absorption rate, and promote the recovery of recurrent abortion. [ABSTRACT FROM AUTHOR]

Simple Summary: In human cancers, there are molecular changes associated with their development and responses to therapy. These include changes in molecules in their membranes called sphingolipids. Understanding why and how these lipids are altered may lead to new therapies targeting these changes. Unfortunately, as in other areas of modern cancer research, we lack an understanding of how these molecules are altered in tumors of Black Americans, or whether these changes have different impacts than in White Americans. As an important first step, we used mass spectrometry to profile the sphingolipids in tumors of the colon, liver, lung, head and neck, and endometrial cancers of Black and White Americans. We found that sphingolipids with known roles in how tumors grow and respond to therapy are differentially altered in Black and White Americans. These results strongly support further research designed to determine if Black Americans may benefit from therapies that target these alterations. 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. [ABSTRACT FROM AUTHOR]

Introduction: There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGOESTRO 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. [ABSTRACT FROM AUTHOR]

Background: Abnormal uterine bleeding (AUB) that is any irregularity in menstrual cycles causes women to refer to clinics. This study aimed to compare the efficacy, safety, and complications of endometrial ablation by the thermal balloon (Cavaterm) method with the hysteroscopy loop resection method in the treatment of AUB. Materials and Methods: The present study is an open-label, randomized clinical trial that was performed in the two hospitals, Shahid Akbarabadi and Hazrat Rasoul Akram, of Tehran, Iran, from December 2019 to October 2020. Patients were randomly allocated to the two groups of interventions by a simple randomization method. The proportion of amenorrhea (as primary outcome) and consequent hysterectomy and patient satisfaction (as secondary outcomes) was assessed using the Chi-square test and independent t test. Results: There was no significant difference between the two groups in the baseline characteristics. The percentage of intervention failure was statistically higher in the hysteroscopy group (24%) in comparison with the Cavaterm group [8.2%, P=0.03, relative risk (RR)=1.63, 95% confidence interval (CI): 1.13-2.36]. Mean ± standard deviation of satisfaction based on the Likert score in the Cavaterm group and hysteroscopy group were 4.3 ± 1.21 and 3.7 ± 1.56, respectively, that showed a significant difference (P=0.04). Assessing the procedural complications, the rate of spotting, bloody discharge, and malodor discharge was significantly higher in the Cavaterm group. In contrast, postoperative dysmenorrhea is more common in the hysteroscopy group. Conclusion: Cavaterm ablation is accompanied by a higher success rate of amenorrhea and patients' satisfaction than hysteroscopy ablation (registration number: IRCT20220210053986N1). [ABSTRACT FROM AUTHOR]

Background: The Surgical staging of endometrial cancer includes a hysterectomy, bilateral salpingo-oophorectomy, and estimation of regional LN involvement, specially the pelvic and aortic lymph node. Some advised that lymphadenectomy explains the risk of recurrence and helps clinicians make the decision to give adjuvant treatment to high-risk patients. While, some suggested that, complete pelvic and para-aortic lymphadenectomy itself is associated with major comorbidities. Sentinel lymphadenectomy has been suggested in the staging process of the diseases. The aim of this study was to compare the role SLN mapping over total lymphadenectomy for detection of disease metastasis in cases of cancer of the endometrium. Method: 30 patients that were diagnosed of having endometrial cancer based on biopsy were included in this study and were divided in to two equal groups and mapping of sentinel lymph nodes was done to 15 patients and all patients had undergone lymphadenectomy. Results: In this study The mean age of patients was 55 years (range 45-74) for group 1 and was 56ys (range 43-75) for group2. Also the increase in weight as BMI, Median (Range) was 35 (26-45) for group 1 and for group2 was 34 (28-50)... And shown in our study there is no significant difference between both groups regarding BMI, age, clinical, family history and preoperative pathological results. we approved that proved that SLN biopsy has relatively equal values like lymphadenectomy in staging of endometrial cancer with sensitivity 80% and specificity 90%. Sentinel mapping had good sensitivity and specificity diagnostic potentials. [ABSTRACT FROM AUTHOR]

Howard L Curlin, Ted L Anderson Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, USACorrespondence: Howard L Curlin, Email howard.curlin@vumc.orgStudy Objective: To examine long-term outcomes from the pivotal study that evaluated the safety and effectiveness of the Cerene® Cryotherapy Device (Channel Medsystems, Berkeley, CA) in premenopausal women with heavy menstrual bleeding due to benign causes who have completed childbearing.Methods: The prospective, multicenter, single-arm, open-label study had eight sites in the USA, one in Mexico, and two in Canada. Inclusion criteria included uterine sound ≤ 10 cm, endometrial cavity length 2.5 to 6.5 cm, age 25 to 50 years, a pictorial blood loss assessment chart score of ≥ 150, no submucosal myomata and/or uterine obstruction, distortion, or abnormality. A total of 242 subjects underwent a 2.5-minute cryoablation. Long-term follow-up visits were conducted at Month 24 and Month 36. Data collected included gynecological adverse events, description of last menstrual period, contraception status, self-report of pregnancy, medical or surgical interventions to treat abnormal uterine bleeding, satisfaction, recommendation, and quality of life (QoL). QoL outcomes were measured with the Menorrhagia Impact Questionnaire (MIQ) and the Premenstrual Symptoms Impact Survey (PMSIS™).Results: 201 subjects completed their Month 36 final study visit. Subject outcomes were comparable to those at Month 12. Eighty-nine percent of subjects reported amenorrhea, a lighter-than-normal, or normal period, 91% of subjects had no or slight limitations in MIQ measured activities, and 85% reported premenstrual symptoms at a low frequency. Eighty-five percent of the subjects were satisfied or very satisfied. The cumulative incidence of hysterectomy was 5% and reintervention was 8.7%. Forty-nine gynecologic adverse events (AE) were reported; one non-serious AE, postcoital bleeding, was reported as related to the procedure. No serious device-related or procedure-related AEs were reported.Conclusion: Study data demonstrate that the positive effects of Cerene Cryotherapy Device treatment are sustained through Month 36 and that the risks associated with the device and procedure are low (ClinicalTrials.gov; NCT02842736).Keywords: ablation, endometrial, menorrhagia, cryotherapy

Determining whether endometrial microbial isolates are pathogens, contaminants, or even part of the “normal” microbiome is extremely complex, particularly given the absence of “gold standard” tests for endometritis. Population-level benchmarking and temporal monitoring can provide novel insights and a wider context to improve understanding. This study aimed to (i) estimate the prevalence of endometrial isolates from swabs of Thoroughbred broodmares in Newmarket, UK between 2014 and 2020; and (ii) evaluate the effects of year, mare age, and cytology findings on isolate prevalence. Generalised linear mixed models with a logit link, both null models and models using year of sampling, mare age, or cytology findings as predictors, were fitted to estimate isolate prevalence. Over the 7-year period, data were available from 18,996 endometrial-swab samples from 6050 mares on 290 premises. The overall isolate prevalence was 35.5% (95% confidence interval (CI) 33.0–37.9), and this varied significantly between years. The most prevalent isolates were β-hemolytic Streptococcus (17.9; 95% CI: 17–19) and E. coli (10.3%; 95% CI: 9.0–11.6). Isolate prevalence increased with mare age except for E. coli isolates, and with increasing category of cytology findings except for α-hemolytic Streptococcus isolates. The results provide novel estimates of isolate prevalence and highlight knowledge gaps around potential complexities in the interpretation of findings.