Uterine Specimens Research Articles

Association Among Surgeon Volume, Surgical Approach, and Uterine Size for Hysterectomy for Benign Indications.

To assess the relationship between surgeon volume and surgical approach for patients undergoing hysterectomy for benign indications among uteri of varying sizes. This was a retrospective cohort study of patients who underwent hysterectomy for benign indications from 2012 to 2021 within the Michigan Surgical Quality Collaborative registry. For each hysterectomy, the relative annual volume of the performing surgeon was assessed by calculating the proportion of hysterectomy cases contributed by the surgeon each calendar year relative to the total number of hysterectomies in the registry for that year. Hysterectomies were stratified into tertiles: those performed by low-volume surgeons, intermediate-volume surgeons, and high-volume surgeons. Uterine size was represented by the uterine specimen weight and categorized to facilitate clinical interpretation. Multivariable logistic regression models were developed incorporating interaction terms for surgeon volume and uterine size to explore potential effect modification. A total of 54,150 hysterectomies were included. Hysterectomies performed by intermediate- and high-volume surgeons were more likely to be performed through a minimally invasive approach compared with those performed by low-volume surgeons (intermediate-volume: adjusted odds ratio [aOR] 1.68, 95% CI, 1.47-1.92; high-volume: aOR 2.14, 95% CI, 1.87-2.46). Moreover, this likelihood increased with increasing uterine weight. For uteri weighing between 1,000 g and 1,999 g, the odds of minimally invasive approach was significantly higher among intermediate-volume surgeons (aOR 3.38, 95% CI, 2.04-5.12) and high-volume (aOR 9.26, 95% CI, 5.64-15.2) surgeons, compared with low-volume surgeons. After including an interaction term for uterine weight and surgeon volume, we identified effect modification of surgeon volume on the relationship between uterine size and choice of minimally invasive surgery. For uteri up to 3,000 g in weight, hysterectomies performed by high-volume surgeons have a higher likelihood of being performed through a minimally invasive approach compared with those performed by low-volume surgeons.

Identification of 10 differentially expressed genes involved in the tumorigenesis of cervical cancer via next-generation sequencing.

The incidence and mortality of cervical cancer remain high in female malignant tumors worldwide. There is still a lack of diagnostic and prognostic markers for cervical carcinoma. This study aimed to screen differentially expressed genes (DEGs) between normal and cervical cancer tissues to identify candidate genes for further research. Uterine cervical specimens were resected from our clinical patients after radical hysterectomy. Three patients' transcriptomic datasets were built by the next generation sequencing (NGS) results. DEGs were selected through the edgeR and DESeq2 packages in the R environment. Functional enrichment analysis, including GO/DisGeNET/KEGG/Reactome enrichment analysis, was performed. Normal and cervical cancer tissue data from the public databases TCGA and GTEx were collected to compare the expression levels of 10 selected DEGs in tumor and normal tissues. ROC curve and survival analysis were performed to compare the diagnostic and prognostic values of each gene. The expression levels of candidate genes were verified in 15 paired clinical specimens via quantitative real-time polymerase chain reaction. There were 875 up-regulated and 1,482 down-regulated genes in cervical cancer samples compared with the paired adjacent normal cervical tissues according to the NGS analysis. The top 10 DEGs included APOD, MASP1, ACKR1, C1QTNF7, SFRP4, HSPB6, GSTM5, IGFBP6, F10 and DCN. GO, DisGeNET and Reactome analyses revealed that the DEGs were related to extracellular matrix and angiogenesis which might influence tumorigenesis. KEGG enrichment showed that PI3K-Akt signaling pathway might be involved in cervical cancer tumorigenesis and progression. The expression levels of selected genes were decreased in tumors in both the public database and our experimental clinical specimens. All the candidate genes showed excellent diagnostic value, and the AUC values exceeded 0.90. Additionally, APOD, ACKR1 and SFRP4 expression levels could help predict the prognosis of patients with cervical cancer. In this study, we selected the top 10 DEGs which were down-regulated in cervical cancer tissues. All of them had dramatically diagnostic value. APOD, ACKR1 and SFRP4 were associated with the survivals of cervical cancer. C1QTNF7, HSPB6, GSTM5, IGFBP6 and F10 were first reported to be candidate genes of cervical carcinoma.

Molecular classification of endometrial carcinoma on endometrial biopsy: an early prognostic value to guide personalized treatment

ObjectiveMolecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the...

Impact of uterine weight on surgical outcomes in robotic hysterectomy: An ambispective analysis.

Robot-assisted surgeries are increasingly used for the treatment of benign gynaecological conditions. However, their impact in cases of significantly enlarged uteruses remains uncertain. This study aims to investigate whether the weight of the uterus influences the surgical results of robotic hysterectomy. Ambispective analysis of 306 cases was performed, of which 265 cases were analysed retrospectively. The outcome measures included total operative time, including docking time, console time and vault closure time, complication rates and quality of life (World Health Organization Quality of Life Brief questionnaire) stratified based on uterine sizes into three groups by every 250 g. Of the 306 cases, 76.47% of cases (n = 234) had uterine weight <250 g, 18.30% of cases (n = 56) had uterine weight between 250 and 500 g, while 5.23% of cases (n = 16) had a weight of uterine specimen >500 g. The total operative time was significantly lower in the <250 g group compared to >500 g (81.92 ± 22.81 vs. 111.88 ± 40.27 min; P = 0.003), contributed primarily by the console time. Although the need for post-operative blood transfusion was higher in the >500 g group, the overall complication rate between the three groups was similar. The three groups had comparable QOL through all four domains. The present study underscores the influence of uterine weight on robotic hysterectomy outcomes, revealing increased operative times and post-operative haemoglobin drop for uteri over 500 g. Despite these challenges, complications were not significantly affected by uterine size.

Leiomyomatosis: A Rare Case of Mistaken Identity

Abstract: Diffuse uterine leiomyomatosis (DUL) is a rare benign uterine pathology that is often misdiagnosed as uterine leiomyomas. We present a case of a woman with abnormal uterine bleeding treated with multiple medical therapies without symptomatic relief. She underwent two surgeries, almost a year apart, with the histopathologic diagnosis of leiomyomas. After numerous failed attempts at medical and surgical treatments, the patient requested definitive surgery and underwent a robotic-assisted laparoscopic hysterectomy. Histopathologic analysis of the entire uterine specimen confirmed diffuse uterine leiomyomatosis. Case Report: A 31-year-old female was referred to our office with a history of abnormal uterine bleeding and heavy menstrual bleeding who failed hormonal therapies. Levonorgestrel-releasing intrauterine devices were inserted at two different times and were expelled due to heavy menses. Pelvic magnetic resonance imaging reported leiomyomas. The patient underwent hysteroscopy and a robotic-assisted myomectomy. Pathology revealed leiomyomas. Seven months after her first surgery, her bleeding recurred, and the patient became severely anemic, requiring hospitalization and transfusion of 2 units of packed RBCs. Over a year later, the patient underwent a second hysteroscopic and robotic myomectomy after failed medical therapies of tranexamic acid, progesterone medication, and gonadotropin-releasing hormone antagonist with minimal symptom relief. Her quality of life suffered tremendously due to ongoing AUB-HMB. After seven months, the patient requested definitive surgical therapy and underwent a robotic-assisted laparoscopic hysterectomy. Pathology reported diffuse uterine leiomyomatosis. Diffuse uterine leiomyomatosis is a rare benign uterine pathology that is often misdiagnosed as uterine leiomyomas. Early diagnosis of DUL is challenging and often inconclusive. Less than 50 diffuse uterine leiomyomatosis cases have been reported in the literature. The myometrium in DUL is almost entirely replaced by numerous ill-defined benign smooth muscle tumors. MRI offers mapping of the size, site, and distribution of leiomyomas, but findings are difficult to differentiate from DUL. The pathophysiology of DUL development remains poorly understood, with patients frequently complaining of abnormal uterine bleeding, heavy menstrual bleeding, fertility issues, and dysmenorrhea. DUL is often misdiagnosed as leiomyomas or adenomyosis clinically, given the similarity in manifestations. Leiomyomatosis is histologically characterized by the proliferation of smooth muscle cells forming fascicles and nodules, which blend with normal myometrium tissue. Hysterectomy is the definitive treatment of DUL, with this case report demonstrating the close similarity between the two.

A novel technique for the measurement of cervical length in non-pregnant women.

Cervical elongation is considered a risk factor for pelvic organ prolapse treatment failure in uterine preservation surgery. Consensus has not been reached regarding what is considered a normal cervical length, or how to measure it. Our primary aim was to test a new technique for measuring cervical length. We enrolled women undergoing hysterectomy, with or without pelvic organ prolapse (for all indications except cervical tumours/history of cervical operations). Their cervical lengths were measured both by ultrasound and anatomical measurement. The external length of the cervix was measured using Doppler location of the uterine artery near the cervical-uterine junction as the proximal point and compared to the ultrasound measurement of the cervical canal. The uterine specimen was used to record anatomical cervical measurements as well as uterine corpus length. Baseline characteristics such as age, body mass index and pelvic organ prolapse quantification were also collected. Twenty women were eligible for evaluation. We found the average anatomical cervical canal length was (ccAN) 33.95 mm (range ± 9.23) and by external measurement (ceAN) 36.80 mm (range ± 7.54). We found a significant, high-powered correlation between our ultrasound and anatomical measurements in both techniques, as well as between the two ultrasound techniques. We also found a negative correlation between cervical length and women's age (rp = -0.443, P = 0.05). Transvaginal ultrasound measurement of cervical length using the location of the uterine artery was found to have a strong correlation to the anatomical cervical length and can be used for the measurement of normal cervical length.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience

ObjectiveHysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. MethodsA retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. Results121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. ConclusionOur study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Imaging and molecular features of adenomyosis after menopause

ObjectivesTo explore the imaging features and the molecular characterization of adenomyosis after menopause. Study designAn observational cross-sectional study was performed in a group of postmenopausal patients undergoing a transvaginal ultrasound (TVUS) (n = 468). Among those presenting the US criteria for adenomyosis, also confirmed by magnetic resonance imaging (MRI), previous menstrual symptoms, gynecological and obstetric history were reviewed. In a subgroup undergoing hysterectomy, uterine specimens were analyzed by histology and expression of genes implicated in the epithelial-mesenchymal transition, inflammation and fibrosis, including the sphingosine-1-phosphate (S1P) pathway, was evaluated and compared to matched non-menopausal adenomyosis specimens. Main outcome measuresDirect and indirect US features of adenomyosis according to Morphological Uterus Sonographic Assessment at TVUS. Molecular characterization of postmenopausal versus pre-menopausal adenomyosis samples. ResultsAccording to TVUS and MRI, adenomyosis was identified in 49 patients (10.4 %). On US, diffuse adenomyosis was the most common phenotype, whereas internal adenomyosis with diffuse pattern and asymmetric type was the most prevalent on MRI. Molecular analysis showed that adenomyosis lesions express markers of epithelial-mesenchymal transition, inflammation and fibrosis also in postmenopausal women. By comparing the results with those from pre-menopausal samples, the expression of α smooth muscle actin (αSMA), a marker of fibrosis, was significantly greater after menopause, and altered S1P catabolism and signaling were observed. ConclusionsAdenomyosis may be identified in postmenopausal women by imaging, either TVUS or MRI, and fibrosis is one of the key features on molecular analysis.

Uterine scars after caesarean delivery: From histology to the molecular and ultrastructural level.

Uterine rupture during a trial of labor after caesarean delivery (CD) is a serious complication for mother and fetus. The lack of knowledge on histological features and molecular pathways of uterine wound healing has hindered research in this area from evolving over time. We analysed collagen content and turnover in uterine scars on a histological, molecular and ultrastructural level. Therefore, tissue samples from the lower uterine segment were obtained during CD from 16 pregnant women with at least one previous CD, from 16 pregnant women without previous CD, and from 16 non-pregnant premenopausal women after hysterectomy for a benign disease. Histomorphometrical collagen quantification showed, that the collagen content of the scar area in uterine wall specimens after previous CD was significantly higher than in the unscarred myometrium of the same women and the control groups. Quantitative real-time PCR of uterine scar tissue from FFPE samples delineated by laser microdissection yielded a significantly higher COL3A1 expression and a significantly lower COL1A2/COL3A1 ratio in scarred uteri than in samples from unscarred uteri. Histological collagen content and the expression of COL1A2 and COL3A1 were positively correlated, while COL1A2/COL3A1 ratio was negatively correlated with the histological collagen content. Transmission electron microscopy revealed a destroyed myometrial ultrastructure in uterine scars with increased collagen density. We conclude that the high collagen content in uterine scars results from an ongoing overexpression of collagen I and III. This is a proof of concept to enable further analyses of specific factors that mediate uterine wound healing.

Chronic Endometritis and Uterine Endometrium Microbiota in Recurrent Implantation Failure and Recurrent Pregnancy Loss.

The aim of this study was to evaluate whether chronic endometritis (CE) and uterine endometrium microbiota were associated with repeated implantation failures (RIFs) and recurrent pregnancy losses (RPLs). In this prospective study, uterine endometrial specimens were obtained from 24 women with RIF, 27 with RPL, and 29 fertile control women. Immunohistochemical staining of CD138 for CE and 16S ribosomal RNA (rRNA) sequencing analysis for uterine endometrium microbiota were performed simultaneously. To assess CE, Liu's method, McQueen scores and plasma cell count/10 mm2 were used. The frequency of CE (plasma cells > 5.15/10 mm2) was higher in women with RPL (29.6%) than in fertile controls (6.8%, p < 0.05). The plasma cell count/10 mm2 in women with RPL (median 1.53, range 0-252.6, p < 0.01) and women with RIF (median 0.6, range 0-6.98, p < 0.05) was higher than in fertile controls (median 0, range 0-29). The uterine endometrium microbiota in women with RPL or RIF was not significantly different from that in fertile controls. However, the relative dominance rate of Lactobacillus iners (median 4.7%, range 0-99.9 vs. median 0%, range 0-100, p < 0.001) and the positive rate of Ureaplasma species (36.3% vs. 8.6%, p < 0.05) were higher in 11 women with CE than in 69 women without CE. The results suggest that CE may be involved in the pathophysiology of RPL and RIF. Lactobacillus iners and Ureaplasma species may be associated with the etiology of CE.

Polarimetric imaging for cervical pre-cancer screening aided by machine learning: ex vivo studies.

Wide-field imaging Mueller polarimetry is an optical imaging technique that has great potential to become a reliable, fast, non-contact in vivo imaging modality for the early detection of, e.g., deceases and tissue structural malformations, such as cervical intraepithelial neoplasia, in both clinical and low-resource settings. On the other hand, machine learning methods have established themselves as a superior solution in image classification and regression tasks. We combine Mueller polarimetry and machine learning, critically assess the data/classification pipeline, investigate the bias arising from training strategies, and demonstrate how higher levels of detection accuracy can be achieved. We aim to automate/assist with diagnostic segmentation of polarimetric images of uterine cervix specimens. A comprehensive capture-to-classification pipeline is developed in house. Specimens are acquired and measured with imaging Mueller polarimeter and undergo histopathological classification. Subsequently, a labeled dataset is created within tagged regions of either healthy or neoplastic cervical tissues. Several machine learning methods are trained utilizing different training-test-set-split strategies, and their corresponding accuracies are compared. Our results include robust measurements of model performance with two approaches: a 90:10 training-test-set-split and leave-one-out cross-validation. By comparing the classifier's accuracy directly with the ground truth obtained during histology analysis, we demonstrate how conventionally used shuffled split leads to an over-estimate of true classifier performance . The leave-one-out cross-validation, however, leads to more accurate performance with respect to newly obtained samples that were not used to train the models. Combination of Mueller polarimetry and machine learning is a powerful tool for the task of screening for pre-cancerous conditions in cervical tissue sections. Nevertheless, there is a inherent bias with conventional processes that can be addressed using more conservative classifier training approaches. This results in overall improvements of the sensitivity and specificity of the developed techniques for "unseen" images.

The Need for Presurgical Evaluation for Placenta Accreta Spectrum.

Staging or grading of placenta accreta spectrum has historically relied on histopathologic evaluation of placental and uterine specimens. This approach has limited utility, since it is retrospective in nature and does not allow for presurgical planning. Here, we argue for a paradigm shift to use of clinical and imaging characteristics to define the presurgical stage. We summarize past attempts at staging, and define a new data-driven approach to determining the stage prior to delivery. Use of this model may help hospitals direct patients to the most appropriate level of care for workup and management of placenta accreta spectrum. KEY POINTS: · Staging systems that rely on histopathologic grade (accreta, increta, percreta) are unhelpful in antenatal planning for placenta accreta spectrum.. · Past attempts at pre-delivery (pre-surgical) staging have failed to account for key factors that contribute to risk and morbidity.. · We developed a data-driven model that could be easily incorporated as a decision aid into clinical practice to help clinicians decide an individual patient's risk for placenta accreta spectrum..

Rates of unanticipated premalignant and malignant lesions at the time of hysterectomy performed for pelvic organ prolapse in an underscreened population

The rate of unanticipated premalignant or malignant pathology at the time of hysterectomy performed for pelvic organ prolapse has been previously reported to be 0.2%. It is not known whether this rate is similar in patients with limited access to regular medical care. This study aimed to describe the rates of unanticipated premalignancy and malignancy at the time of hysterectomy performed for pelvic organ prolapse in an underscreened population and to determine the risk factors for unanticipated pathology. Hysterectomies performed for pelvic organ prolapse at a large public hospital between July 2007 and July 2019 were reviewed. Patients undergoing surgery for malignancy or premalignancy were excluded. Medical records were reviewed for demographic information, medical history, preoperative workup, and final pathology. Frequencies of abnormal pathologies were calculated. Demographic and screening factors were correlated with pathologic findings using the Fisher exact test or Mann-Whitney U test, as appropriate. This study was approved by the institutional review board. Between 2007 and 2019, 759 cases of pelvic organ prolapse were identified. Of 759 patients, 667 (87.9%) self-identified as Hispanic. The median age was 57 years old, and 505 of 759 patients (66.5%) were in the postmenopausal stage. Abnormal uterine bleeding history was present in 217 of 759 patients (28.6%). Of 759 patients, 493 (65.4%) underwent preoperative ultrasonography, and 290 (38.3%) underwent preoperative endometrial biopsy. Of the 744 uterine specimens that had available histology results, there were 2 cases of endometrial hyperplasia and 1 case of endometrial cancer. Of the 729 cervical specimens that were available for review, there was 1 case of intraepithelial neoplasia and 2 cases of cervical cancer. In the 246 patients who underwent oophorectomy, no ovarian malignancy was found. For patients undergoing hysterectomy for pelvic organ prolapse in an underscreened population, the rates of endometrial dysplasia or cancer were 0.40% (3/744), and the rates of cervical dysplasia or cancer were 0.42% (3/729). Our results underscore the importance of considering screening history when interpreting preoperative cervical and endometrial cancer screening. Consideration of higher negative predictive value tests, such as cytology with human papillomavirus cotesting and preoperative counseling on the risks and management strategies of unanticipated premalignancy or malignancy within this population may be reasonable.

Chronic endometritis and endometrial microsatellite instability: is there a connection?

Introduction One of the criteria of impaired DNA repair is microsatellite instability (MSI) resulting from functional insufficiency of the mismatched nucleotide repair (MMR) system, a complex of proteins (MLH-1, PMS- 2, MSH-2, MSH-6). No data on the study of MSI in chronic endometritis (CE) were found in the available literature.The aim of the study was to determine the structural features of microsatellite instability in the endometrium in female patients with chronic inflammation of the uterine mucosa.Materials and methods Group I consisted of 30 women with morphologically confirmed high-grade CE; Group II consisted of 30 patients with low-grade CE; Group III consisted of 30 women who sought pregnancy planning and had histologically unchanged endometrium. The degree of CE in patients in groups I and II was variable. We analyzed the expression levels of MLH-1-, MSH- 2-, MSH-6-, and PMS-2-proteins in the endometrium by estimating the staining area of nuclei and cytoplasm of the affected cells over the entire slice area. Nonparametric statistical methods with Mann-Whitney test were used. The value of probability of error was set at 0.05.Results There was a statistically significant decrease in the level of MMR protein expression in the endometrial samples from the Group I patients compared to the same indices in the Group II and III women. No statistically significant results were found when analyzing the level of MMR protein expression depending on the severity degree of CE.Discussion There was a statistically significant decrease in the expression level of the markers studied (MLH-1, PMS-2, MSH-2, MSH-6) in endometrial specimens from patients with low-activity CE compared to uterine mucosa biopsy specimens from highly active CE and mid-stage endometrial secretion phase specimens. The described morphological features of the uterine mucosa in patients with low-activity CE are consistent with the findings of other authors. The literature provides indications of structural features of MSI in pre-tumor and tumor processes in the uterine mucosa.Conclusion Endometrial samples with low activity and various degrees of CE show statistically significantly lower expression levels of MLH-1, PMS-2, MSH-2, MSH-6 when compared to biopsy specimens from highly active CE and normal endometrial samples, which may indicate pathogenetic heterogeneity in the development of inflammation in the endometrium.

Expression of CD47 and its ligands in pregnant mice infected with Toxoplasma gondii during pregnancy

Expression of CD47 and its ligands in pregnant mice infected with Toxoplasma gondii during pregnancy

Current Non-Invasive Imaging Techniques Used in the Diagnosis of Adenomyosis

Objective: This review aims to provide insights into the current non-invasive imaging methods used in the diagnosis of adenomyosis, as well as to highlight their diagnostic accuracy, advantages, disadvantages and limitations in the detection of this benign uterine condition. At the same time, this paper emphasizes the importance of using consensus-based terminology in the imaging description of these lesions. Mechanism: A search of PUBMED database was conducted for articles published between January 1998 and August 2022 and studies which compared non-invasive imaging methods with postoperative histology examination of uterine specimens were primarily selected. Transvaginal two-dimensional ultrasound was for a long time the main non-invasive imagistic method used for assessment of adenomyosis lesions. The introduction of Morphological Uterus Sonographic Assessment (MUSA) group criteria yielded a significantly better diagnostic outcome of adenomyosis in case of conventional ultrasonography, but the distinction of concomitant benign uterine conditions still remained challenging. Findings in Brief: The addition of three-dimensional ultrasound or elastosonography to conventional two-dimensional transvaginal ultrasound yielded higher diagnostic sensitivity. Qualitative elastography particularly proved useful in the diagnosis of adenomyosis due to its capacity to achieve differential diagnosis of benign uterine pathologies based on lesion stiffness. Magnetic resonance imaging (MRI) examination presents higher diagnostic specificity and sensitivity, can assess the endometrial and myometrial layers in detail, but its use has been shadowed by costs and significantly longer examination time. Conclusions: The imaging terminology established by consensus by the MUSA group in recent years has facilitated the description of adenomyosis-specific lesions. Two-dimensional transvaginal ultrasound in combination with three-dimensional ultrasound or combined with qualitative elastography offers similar diagnostic sensitivity and specificity to MRI. Despite some limitations, MRI remains a reliable diagnostic method for adenomyosis.

Cytopathological features associated with POLE mutation in endometrial cancer.

For patients with endometrial cancer, the POLE (polymerase epsilon) mutation (POLEmut)-subtype, one of four molecular-analysis-based categories in the Cancer Genome Atlas (TCGA), has the best prognosis. The following histological characteristics are typically observed in endometroid carcinoma cases with the POLEmut-subtype: (1) the presence of tumour giant cells, (2) numerous tumour-infiltrating lymphocytes (TILs) and/or peri-tumoral lymphocytes, and (3) a high grade. However, in the context of cytology, the morphological characteristics of this subtype remain unknown. DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues was subjected to next-generation sequencing analysis and categorised according to the TCGA classifications. Genomic mutation, tumour mutation burden (TMB), and microsatellite instability were also assessed. Cytological specimens of resected uteri obtained using the Papanicolaou method were histologically separated into three types. Seven out of 112 patients (6%) with endometrial cancer were diagnosed with the POLEmut-subtype between January 2019 and August 2021. Tumour giant cells were observed in three cases (43%) on histology and cytology. TIL and/or peritumoral lymphocytes with inflammatory cells were detected in five cases (71%) on histology and three cases (43%) on cytology. Cases in which these three characteristics were observed on both cytology and histology may have belonged to the POLEmut-subtype. There were no cases in which these characteristics were absent on histology but present on cytology. TMB tended to be higher in cases when the three characteristics were observed in both cytological and histological findings. Preoperative endometrial cytology highlighted the characteristics of the POLEmut-subtype in the histological analysis of resected uterine specimens and has the potential to play an important role in treatment decisions.

Can biomarkers identified from the uterine fluid transcriptome be used to establish a noninvasive endometrial receptivity prediction tool? A proof-of-concept study

BackgroundEmbryo implantation in a receptive endometrium is crucial for successful pregnancy. Endometrial receptivity (ER) prediction tools based on endometrial transcriptome biomarkers by endometrial biopsy have been used to guide successful embryo implantation in in vitro fertilization (IVF) patients. However, no reliable noninvasive ER prediction method has been established, and one is greatly needed. We aimed to identify biomarkers from uterine fluid transcriptomic sequencing data for establishing noninvasive ER prediction tool and to evaluate its clinical application potential in patients undergoing IVF.MethodsThe non-invasive RNA-seq based endometrial receptivity test (nirsERT) was established by analyzing transcriptomic profile of 144 uterine fluid specimens (LH + 5, LH + 7, and LH + 9) at three different receptive status from 48 IVF patients with normal ER in combination with random forest algorithm. Subsequently, 22 IVF patients who underwent frozen-thaw blastocyst transfer were recruited and analyzed the correlation between the predicted results of nirsERT and pregnancy outcomes.ResultsA total of 864 ER-associated differentially expressed genes (DEGs) involved in biological processes associated with endometrium-embryo crosstalk, including protein binding, signal reception and transduction, biomacromolecule transport and cell-cell adherens junctions, were selected. Subsequently, a nirsERT model consisting of 87 markers and 3 hub genes was established using a random forest algorithm. 10-fold cross-validation resulted in a mean accuracy of 93.0%. A small cohort (n = 22) retrospective observation shows that 77.8% (14/18) of IVF patients predicted with a normal WOI had successful intrauterine pregnancies, while none of the 3 patients with a displaced WOI had successful pregnancies. One patient failed due to poor sequencing data quality.ConclusionsNirsERT based on uterine fluid transcriptome biomarkers can predict the WOI period relatively accurately and may serve as a noninvasive, reliable and same cycle test for ER in reproductive clinics.Trial registrationChinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.

Prevalence of infection with Trichomonas vaginalis in Tikreet city, Salah Al-Deen province

During the period from November 2008 till the end of February 2009, the present study was carried on. A total of 105 vaginal and uterine specimens, of married females attended Tikreet teaching Hospital and private laboratories in Tikreet city, was collected and examined. The examination results revealed that 24 women were infected (22.86%). The highest prevalence of infection (35.00%) was in the age group 16-20, with absence of infection in the women aged more than 41 year. It has been observed that the highest prevalence of infection (13.33%) was recorded in the illiterate women, and recorded lower prevalence of infection (0.95%) in women with higher academic achievement. Also, recorded the highest prevalence of infection in rural women (15.24%) compared with women in urban (7.62%). Also, in the present study noted a relationship between the infection with pregnancy and the number of children, the results show that the highest prevalence of infection (7.62%) were in the women without children, whereas the lower prevalence of infection (3.80%) were among the women have six children. Also, the highest prevalence of infection (20.00%) were in the women has not use contraception, compared with women used contraceptive materials. It has been observed the irritation and inflammation in the sites of infection with thick, yellowish-green and foul smell secretions with red blood cells, pus and epithelial cells.

TEM1 up-regulates MMP-2 and promotes ECM remodeling for facilitating invasion and migration of uterine sarcoma

ObjectivesTo explore the correlation between tumor endothelial marker 1 (TEM1) and matrix metalloproteinase 2 (MMP-2) in uterine sarcoma and their roles in the progression of uterine sarcoma.MethodsUterine leiomyosarcoma (uLMS, n = 25) and uterine leiomyoma (n = 25) specimens were collected from a total of 50 patients. Immunohistochemistry assay was conducted to determine the expression of TEM1, MMP-2 and MMP-9. TEM1 over expression (hTEM1) and low expression (shRNA-TEM1) MES-SA cell lines were established as in vitro uterine sarcoma models. MMP-2 mRNA, protein expression and enzymatic activity were verified using qPCR, Western blot and gelatin zymography respectively. MMP-2 expression was downregulated using MMP-2 siRNA in hTEM1 MES-SA cells to better study the role of MMP-2. The invasive and migratory capacities of hTEM1, shRNA-TEM1, and hTEM1 treated with MMP-2 siRNA MES-SA cells were determined using transwell assays. Extracellular matrix (ECM) remodeling mediated by TEM1 was examined using cell-ECM adhesion and fluorescent gelatin-ECM degradation assays. The immunofluorescence of F-actin was examined to analyze the formation of invadopodia. Subcutaneous and intraperitoneal xenografts were established to validate the role of TEM1 in promoting uterine sarcoma metastasis.ResultsTEM1 and MMP-2 were expressed in 92% (n = 23) and 88% (n = 22) of uterine leiomyosarcoma specimens, respectively. Both TEM1 and MMP-2 were highly expressed in 100% (n = 17) of high stage (III-IV) uterine leiomyosarcoma specimens. In addition, TEM1 expression was positively correlated with MMP-2 expression in uterine leiomyosarcoma. The successful establishment of in vitro uterine sarcoma models was confirmed with qPCR and Western blotting tests. TEM1 promoted the invasion and metastasis of uterine sarcoma in vivo and in vitro. MMP-2 expression and activity were up-regulated in hTEM1 cells but down-regulated in shRNA-TEM1 cells. Importantly, MMP-2 knockdown impaired the invasive and migratory capacity of hTEM1 cells. TEM1 promoted ECM remodeling by increasing cell-ECM adhesion and ECM degradation. TEM1 overexpression also induced the formation of invadopodia.ConclusionTEM1 was co-expressed and positively correlated with MMP-2 in uterine leiomyosarcoma specimens. In addition, both TEM1 and MMP-2 were associated with tumor development. TEM1 promoted uterine sarcoma progression by regulating MMP-2 activity and ECM remodeling.