Lymphedema self-assessment among endometrial cancer survivors.

PURPOSE: Lower extremity lymphedema (LEL), which causes ankle, leg, and feet swelling, poses a significant challenge for endometrial cancer survivors, impacting physical functioning and psychological well-being. Inconsistent LEL diagnostic methods result in wide-ranging LEL incidence estimates. METHODS: We calculated the cumulative incidence of LEL based on survivor-reported Gynecologic Cancer Lymphedema Questionnaire (GCLQ) responses in addition to survivor- and nurse-reported leg circumference measurements among a pilot sample of 50 endometrial cancer survivors (27 White, 23 Black) enrolled in the ongoing population-based Carolina Endometrial Cancer Study. RESULTS: Self-leg circumference measurements were perceived to be difficult and were completed by only 17 survivors. Diagnostic accuracy testing measures (sensitivity, specificity, positive and negative predictive value) compared the standard nurse-measured ≥ 10% difference in leg circumference measurements to GCLQ responses. At a mean of ~11 months post-diagnosis, 54% of survivors met established criteria for LEL based on ≥ 4 GCLQ cutpoint while 24% had LEL based on nurse-measurement. Percent agreement, sensitivity, and specificity approximated 60% at a threshold of ≥ 5 GCLQ symptoms. However, Cohen's kappa, a measure of reliability that corrects for agreement by chance, was highest at ≥ 4 GCLQ symptoms (κ = 0.27). CONCLUSION: Our findings emphasize the need for high quality measurements of LEL that are feasible for epidemiologic study designs among endometrial cancer survivors. Future studies should use patient-reported survey measures to assess lymphedema burden and quality of life outcomes among endometrial cancer survivors.

Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls.

AIMS: NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry to distinguish NTRK-rearranged sarcoma from its mimics. METHODS AND RESULTS: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity. CONCLUSION: Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation.

Utility of ADC Values for Differentiating Uterine Sarcomas From Leiomyomas: Systematic Review and Meta-Analysis.

BACKGROUND. Uterine sarcomas are rare; however, they display imaging features that overlap those of leiomyomas. The potential for undetected uterine sarcomas is clinically relevant because minimally invasive treatment of leiomyomas may lead to cancer dissemination. ADC values have shown potential for differentiating benign from malignant uterine masses. OBJECTIVE. The purpose of this study was to perform a systematic review of the diagnostic performance of ADC values in differentiating uterine sarcomas from leiomyomas. EVIDENCE ACQUISITION. We searched three electronic databases (the MEDLINE, Embase, and Cochrane databases) for studies distinguishing uterine sarcomas from leiomyomas using MRI, including ADC values, with pathologic tissue confirmation or imaging follow-up used as the reference standard. Data extraction and QUADAS-2 quality assessment were performed. Sensitivity and specificity were pooled using hierarchical models, including bivariate and hierarchical summary ROC models. Metaregression was used to assess the impact of various factors on heterogeneity. EVIDENCE SYNTHESIS. Twenty-one studies met the study inclusion criteria. Pooled sensitivity and specificity were 89% (95% CI, 82-94%) and 86% (95% CI, 78-92%), respectively. The area under the summary ROC curve was 0.94 (95% CI, 0.92-0.96). The context of the ADC interpretation (i.e., used as a stand-alone assessment vs integrated as part of multiparametric MRI [mpMRI]) was the only factor found to account significantly for heterogeneity (p = .01). Higher specificity (95% [95% CI, 92-99%] vs 82% [95% CI, 75-89%]) and similar sensitivity (94% [95% CI, 89-99%] vs 88% [95% CI, 82-93%]) were observed when ADC was evaluated among mpMRI features rather than as a stand-alone ADC assessment. ADC cutoff values ranged from 0.87 to 1.29 × 10-3 mm2/s but were not associated with statistically different performance (p = .37). Pooled mean ADC values for sarcomas and leiomyomas were 0.904 × 10-3 mm2/s and 1.287 × 10-3 mm2/s, respectively. CONCLUSION. As part of mpMRI evaluation of uterine masses, a mass ADC value of less than 0.904 × 10-3 mm2/s may be a useful test-positive threshold for uterine sarcoma, consistent with the findings of a prior expert consensus statement. Institutional protocols may influence locally selected ADC values. CLINICAL IMPACT. Using ADC as part of mpMRI assessment improves detection of uterine sarcoma, which could influence candidate selection for minimally invasive treatments. TRIAL REGISTRATION. Prospective Register of Systematic Reviews CRD42024499383.

Vibrational Biospectroscopy: An Alternative Approach to Endometrial Cancer Diagnosis and Screening.

Endometrial cancer (EC) is the sixth most common cancer and the fourth leading cause of death among women worldwide. Early detection and treatment are associated with a favourable prognosis and reduction in mortality. Unlike other common cancers, however, screening strategies lack the required sensitivity, specificity and accuracy to be successfully implemented in clinical practice and current diagnostic approaches are invasive, costly and time consuming. Such limitations highlight the unmet need to develop diagnostic and screening alternatives for EC, which should be accurate, rapid, minimally invasive and cost-effective. Vibrational spectroscopic techniques, Mid-Infrared Absorption Spectroscopy and Raman, exploit the atomic vibrational absorption induced by interaction of light and a biological sample, to generate a unique spectral response: a "biochemical fingerprint". These are non-destructive techniques and, combined with multivariate statistical analysis, have been shown over the last decade to provide discrimination between cancerous and healthy samples, demonstrating a promising role in both cancer screening and diagnosis. The aim of this review is to collate available evidence, in order to provide insight into the present status of the application of vibrational biospectroscopy in endometrial cancer diagnosis and screening, and to assess future prospects.

Metastatic endometrial stromal sarcoma: A rare cause of right-sided intracardiac mass.

The endometrial stromal sarcoma (EES) is a rare uterine malignancy and its intracardiac metastasis are exceedingly rare. We report a case of a 53-year-old female patient diagnosed with a metastatic tumor of a ESS in the right side of the heart, who underwent successful surgical resection and initiated chemotherapy with docetaxel and gemcitabine. At a 9-month follow-up, the patient was in New York Heart Association-Class I, without any further complications.

Ectopic hyperprolactinaemia due to a malignant uterine tumor resembling ovarian sex cord tumors (UTROCST).

PURPOSE: Moderate hyperprolactinaemia (2-5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. METHODS: We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. RESULTS: Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. CONCLUSIONS: Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.

Lesion-targeted cytology to improve cytological sampling for atypical polypoid adenomyomas of the uterus: A case series and review of the literature.

OBJECTIVE: Atypical polypoid adenomyomas (APAs) are uncommon tumours consisting of atypical endometrioid glands and fibromyomatous stroma. Identifying the biphasic nature of atypical glandular components and spindle mesenchymal components without atypia is crucial for the cytological diagnosis of APA. We investigated the utility of lesion-targeted cytology (LTC) to directly collect firm spindle components. METHODS: We recruited seven consecutive surgical patients who underwent cytological examinations before surgery and were diagnosed with APA on postoperative histological examinations. Cytological smears were obtained by routine sampling in five cases and by targeted sampling using transvaginal ultrasonography, that is, LTC, in two cases. We retrospectively analysed the cytological findings from our cases and compared them to those of APA cases previously reported in the English literature. RESULTS: Among 5/7 cases that involved routine cytological sampling, normal cytological findings were found in 2 and atypical glandular cells were found in 3, but spindle cells from mesenchymal components were not detected. In contrast, among 2/7 cases in which sampling involved LTC, spindle cells without atypia, in addition to atypical glandular cells were found. CONCLUSIONS: Lesion-targeted cytology is useful to assess mesenchymal components of APAs and may improve the cytological diagnosis of APA.

Introduction of the MyoSureLITE in an established outpatient hysteroscopy clinic.

BACKGROUND: Endometrial polyps are a common cause of abnormal uterine bleeding. The MyoSureLITE intrauterine morcellation device is effective at resecting endometrial polyps; however, its use in the outpatient setting requires appraisal. AIM: To assess the feasibility, utility, acceptability and costs associated with introduction of the MyoSureLITE into an established outpatient hysteroscopy (OPH) clinic. MATERIAL AND METHODS: A prospective clinical database from a tertiary Melbourne hospital was analysed from 1 July 2015 to 30 June 2018. Three 12-month time periods were compared: pre-introduction and trial phase, early use, and established use of the MyoSureLITE. Wait times, patient acceptability, second OPH bookings and procedure costs were measured. RESULTS: Eight hundred and seventy-one women underwent OPH during the study period, with 238 (27.3%) women presenting with endometrial polyp(s). At each timepoint, 78.5, 25 and 6.3% of women required rebooking for a subsequent hysteroscopy for pathology otherwise suitable for MyoSureLITE resection. Introduction of the MyoSureLITE avoided a subsequent procedure for 4, 60 and 69 women respectively for each year of use, with potentially reduced treatment costs for the institution. Median (IQR) wait time for definitive treatment of intrauterine pathology was 56 (24-84) days at time-period 1, decreasing to 0 (0-0) days during time-period 3, (P < 0.001); 87.6% would undergo OPH again. CONCLUSIONS: Routine use of the MyoSureLITE is effective, feasible, and acceptable to women. Provision of this device in outpatient service allows a 'see-and-treat' model, saving theatre time and treatment costs, facilitating a more direct throughput from presentation to treatment.

Clinical characteristics associated with racial disparities in endometrial cancer outcomes: A surveillance, epidemiology and end results analysis.

OBJECTIVES: Racial disparities exist for endometrial cancer. We examined patterns of care and factors associated with poor outcomes for Black women with endometrial cancer. METHODS: We studied 110,826 endometrial cancer patients diagnosed between 1980 and 2008 with minimum 5years follow-up in the Surveillance, Epidemiology, and End Results database. Trends over time in sociodemographics, disease characteristics and treatment factors were analyzed over four eras: 1980-1989, 1990-1999, 2000-2004, 2005-2008. Using sequential Cox proportional hazards and Fine-Gray competing risk models we determined the association between potential explanatory variables and racial disparities in all-cause mortality (ACM) and cancer-specific mortality (CSM), respectively. RESULTS: Clinical characteristics of Black and White women were relatively constant over time. The unadjusted hazard ratio (HR) among Black women for ACM and CSM were 1.91 (95% CI 1.86-1.97) and 2.35 (95% CI 2.26-2.43), respectively. Adjustment for sociodemographics, disease presentation and surgery decreased the ACM HR to 1.29 (95% CI 1.24-1.34) and CSM HR to 1.18 (95% CI 1.11-1.26) without further decrease from controlling for radiotherapy. Black women were less likely to undergo operative management even when prescribed. Total and radical hysterectomy, and vaginal brachytherapy (VBT) were associated with improved ACM and CSM. Combination VBT and external beam radiotherapy was associated with improved ACM. CONCLUSION: Racial disparities in endometrial cancer survival are predominantly attributable to increased advanced stage, high-grade and aggressive histologic subtype tumors and differential use of surgery in Black women. Intensified surgical and radiation treatment is associated with improved survival, raising questions about treatment adaptations that may potentially reduce survival disparities.

Vaginal metastasis as the initial presentation of leiomyosarcoma: a case report.

BACKGROUND: Uterine leiomyosarcomas are very rare and highly aggressive tumors that have a high rate of recurrence and poor prognosis, even when early diagnosed. Due to their relative rarity, there is limited research on optimal management strategies. CASE PRESENTATION: A 60-year-old woman with a history of an asymptomatic uterine leiomyoma presented in October 2015 with postmenopausal bleeding and a friable vaginal cyst that bled when palpated. A partial cystectomy was performed, and malignant-like cystic and solid components were identified. Histopathology diagnosed an unclassifiable malignant epithelioid tumor. Subsequent imaging studies identified a malignant uterine tumor, a metabolically active vaginal lesion, and two benign leiomyomas. An anterior pelvic exenteration (colpectomy, hysterectomy, bilateral adnexectomy, total cystectomy, and cutaneous ureteroileostomy ad modum Bricker) were performed by laparotomy in March 2016. Examination of the surgical specimens identified a 75 × 75-mm leiomyoma, an 80 × 30-mm infiltrating mesenchymal uterine lesion with vascular invasion and tumor emboli, and a 60 × 30-mm perivascular vaginal tumor. Immunohistochemistry indicated a phenotypic transition from a uterine leiomyosarcoma to a vaginal epithelioid lesion; marker expression changed from the uterine tumor actin+/desmin+/caldesmon+/CD10- phenotype, through the tumor emboli, to an actin-/desmin-/caldesmon-/CD10+ phenotype in the vaginal lesion. A high-grade uterine mesenchymal tumor and vaginal metastasis were diagnosed. Adjuvant chemotherapy with docetaxel, gemcitabine, and doxorubicin commenced in May 2016 and treatment has been well tolerated. CONCLUSIONS: Differentiating leiomyosarcoma from leiomyoma is challenging and few tools other than microscopic evaluation are available. Vaginal compromise in leiomyosarcoma usually results from tumor extension, not hematogenous metastasis. A vaginal metastasis is a very rare initial presentation. We have found only two cases like this described on published literature. The atypical clinical and histological presentation in our case complicated diagnosis and delayed treatment. An early diagnosis and complete surgical clearance gives the best chance of survival, and imaging tools should be applied early in instances of new suspicious malignant lesions.

A clinical analysis of brain metastasis in gynecologic cancer: a retrospective multi-institute analysis.

This study analyzes the clinical characteristics of the brain metastasis (BM) of gynecologic cancer based on the type of cancer. In addition, the study examines the factors influencing the survival. Total 61 BM patients of gynecologic cancer were analyzed retrospectively from January 2000 to December 2012 in terms of clinical and radiological characteristics by using medical and radiological records from three university hospitals. There were 19 (31.1%) uterine cancers, 32 (52.5%) ovarian cancers, and 10 (16.4%) cervical cancers. The mean interval to BM was 25.4 months (21.6 months in ovarian cancer, 27.8 months in uterine cancer, and 33.1 months in cervical cancer). The mean survival from BM was 16.7 months (14.1 months in ovarian cancer, 23.3 months in uterine cancer, and 8.8 months in cervical cancer). According to a multivariate analysis of factors influencing survival, type of primary cancer, Karnofsky performance score, status of primary cancer, recursive partitioning analysis class, and treatment modality, particularly combined therapies, were significantly related to the overall survival. These results suggest that, in addition to traditional prognostic factors in BM, multiple treatment methods such as neurosurgery and combined chemoradiotherapy may play an important role in prolonging the survival for BM patients of gynecologic cancer.

Suction thrombectomy of a uterine carcinosarcoma tumor thrombus extending into the IVC and right atrium.

Uterine carcinosarcoma is a rare, aggressive tumor with several cases in the literature reporting cardiac tumor thrombus involvement. In this case report, we describe a 72-year-old female with a history of uterine carcinosarcoma, who presented with extensive thrombus in the Inferior Vena Cava (IVC) and right atrium. The patient underwent an aspiration thrombectomy which aided in intravascular debulking of the thrombus. Histopathological analysis of the thrombus revealed tumor thrombus. In cryptic cases of tumor thrombus, thrombectomy with histopathological analysis can help confirm the diagnosis of metastatic disease and help guide oncologic staging and further therapy.

Whole-tumor apparent diffusion coefficient histogram analysis for preoperative risk stratification in endometrial endometrioid adenocarcinoma.

OBJECTIVE: To investigate the application of whole-tumor apparent diffusion coefficient (ADC) histogram metrics for preoperative risk stratification in endometrial endometrioid adenocarcinoma (EEA). METHODS: Preoperative MRI of 502 EEA patients were retrospectively analyzed. Whole tumor ADC histogram analysis was performed with regions of interest drawn on all tumor slices of diffusion-weighted imaging scans. Risk stratification was based on ESMO-ESTRO-ESP guidelines: low-, intermediate-, high-intermediate-, and high-risk. Univariable analysis was used to compare ADC histogram metrics (tumor volume, minADC, maxADC, and meanADC; 10th, 25th, 50th, 75th, and 90th percentiles of ADC [recorded as P10, P25, P50, P75, and P90 ADC, respectively]; skewness; and kurtosis) between different risk EEAs, and multivariable logistic regression analysis to determine the optimal metric or combined model for risk stratifications. Receiver operating characteristic curve analysis with the area under the curve (AUC) was used for diagnostic performance evaluation. RESULTS: A decreasing tendency in multiple ADC values was observed from the low- to high-intermediate-risk EEAs. The (low + intermediate)-risk EEAs and low-risk EEAs had significantly smaller tumor volumes and higher minADCs, meanADCs, P10, P25, P50, P75, and P90 ADCs than the (high-intermediate + high)-risk EEAs and non-low-risk EEAs (all P < 0.05), respectively. The combined models of the (meanADC + volume) and the (P75 ADC + volume) yielded the largest AUCs of 0.775 and 0.780 in identifying the (low + intermediate)- and the low-risk EEAs from the other EEAs, respectively. CONCLUSION: Whole-tumor ADC histogram metrics might be helpful for preoperatively identifying low- and (low + intermediate)-risk EEAs, facilitating personalized therapeutic planning.

Clinical Features and Prognostic Factors in Patients With Uterine Leiomyosarcoma: A Single-Center Experience.

Background Uterine leiomyosarcomas (LMS) are associated with more recurrence and higher mortality compared to other uterine cancers. Considering the limited number of case series in the literature, the limited effectiveness of standard treatment methods, and the inadequacy of molecular biomarkers, we planned to investigate the effects of treatment methods and survival outcomes in these patients. Methodology The study was designed retrospectively, and the records of patients who were followed up and treated at Ankara University Faculty of Medicine, Medical Oncology Clinic, between January 1, 2011, and December 31, 2021, were reviewed. Patients over 18 years of age with a pathological diagnosis of uterine LMS were included. Demographic, clinical, and pathological data were recorded using the hospital database. The International Federation of Gynecology and Obstetrics (FIGO) staging was reassessed for each patient in accordance with the AJCC Cancer Staging Manual, Eighth Edition (2017). Tumor size, location, and grade were also evaluated. Types of treatments, protocols, and adverse effects were recorded. Relapsed patients, relapse localization, and treatments given at relapse were recorded and compared.  Results Twenty-eight patients were included. The mean age of the patients was 53.7 years. The median follow-up time was 39.3 months. The localization of LMS could be detected in 22 (78.57%) patients, among them 20 (90.9%) patients had intramural, 1 (4.5%) had submucosal, and 1 (4.5%) had subserosal LMS. All patients (26, 92.8%) underwent primary surgery, except for 2 (7.14%) patients who were metastatic at the time of diagnosis. Adjuvant treatment suggestion was made for 7 (25%) patients with a high risk of recurrence in the multidisciplinary tumor council. Partial response was observed in 1 (3.5%) of the 2 (7.1%) metastatic patients, and stable disease was observed in the other. Recurrence was detected in 22 (84.6%) patients . Fifteen (53.6%) patients died during the follow-up period. Survival was better in premenopausal patients (99.2 versus 51.6 months, P = 0.056). No significant difference was found when the survival of patients who received and did not receive adjuvant treatment were compared. In relapsed patients, there was no significant difference in survival between patients who underwent and did not undergo surgical treatment. Conclusions Uterine LMS is a rare and aggressive malignancy with limited diagnostic methods, frequent recurrences, high mortality, and limited use of nonsurgical treatments. The positive effect of adjuvant treatment on survival has not been demonstrated. Further studies are needed to investigate the effect of hormone receptor status on prognosis and new biomarkers.

Health-related quality of life and patient-reported symptoms after postoperative proton beam radiotherapy of cervical and endometrial cancer: 2-year results of the prospective phase II APROVE-trial.

INTRODUCTION: The APROVE-trial investigated the tolerability of postoperative proton beam therapy in women with cervical or endometrial cancer. The present analysis evaluated the secondary endpoints of health-related quality of life (HRQOL) and patient-reported symptoms. METHODS: 25 patients were included in this prospective phase-II-trial and treated with postoperative radiotherapy using protons alone or in combination with chemotherapy. To attain general and gynecologic-specific HRQOL measures, the EORTC-QLQ-C30 questionnaires combined with -QLQ-CX24 for cervical and -QLQ-EN24 for endometrial cancer were assessed at baseline, at the end of RT and up to 2 years after radiotherapy. The results were compared to an age-matched norm reference population. Symptoms were assessed using Common Terminology Criteria for Adverse Events (CTCAE) and institutional patient-reported symptoms grading. RESULTS: Scores regarding global health status were markedly impaired at baseline (mean: 58.0 ± 20.1) compared to reference population data, but significantly (p = 0.036) improved and evened out to comparable norm values 2 years after proton therapy (mean: 69.9 ± 19.3). Treatment caused acute and long-term worsening of pain (p = 0.048) and gastrointestinal symptoms (p = 0.016) for women with endometrial cancer, but no higher-grade CTCAE ≥ 3° toxicity was observed. Dosimetric evaluation of rectum, sigmoid, large and small bowel showed no correlation with the reported gastrointestinal symptoms. After 2 years, fatigue had significantly improved (p = 0.030), whereas patients with cervical cancer experienced more often lymphedema (p = 0.017). Scores for endometrial cancer pertaining to sexual activity (p = 0.048) and body image (p = 0.022) had improved post treatment; in the latter this effect persisted after 2 years. CONCLUSION: Proton beam therapy in the adjuvant setting was well tolerated with only low-grade side effects concerning gastrointestinal symptoms, lymphedema and pain. Overall quality of life was impaired at baseline, but patients were able to recover to values comparable to norm population 2 years after proton therapy. Larger studies are needed to confirm whether the benefit of proton therapy translates into a clinical effect. Sexual dysfunction remains an important issue. TRIAL REGISTRATION: The trial was registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03184350, 09th June 2017).

Effect of single-dose methotrexate injection to prevent neoplastic changes in high risk complete hydatidiform mole: A randomised control trial.

Background: Complete hydatidiform mole affects women in their reproductive age. About 15-20% develops persistent molar gestational trophoblastic neoplasia (GTN), which is linked with delayed (beyond 56 days) normalization of serum ßHCG after surgical evacuation. Objective: The objective of the article is to shorten the duration of normalization time of ßHCG with single-dose methotrexate injection in women with high risk complete hydatidiform mole (CHM) after suction evacuation. Methods: Total 76 women with CHM were randomized into intervention and control groups. In the intervention arm (n = 34) women received single dose 100 mg intramuscular methotrexate injection post evacuation and the control group (n = 42) had standard care. Surveillance was done in both groups at two weeks intervals for next six months and duration of normalization of ßHCG level was recorded. Results: Total 94.7% women completed follow-up. Mean of normalization time was significantly lower in the intervention group compared to controls (9.7 weeks versus 14.7 week; P < 0.01). Time to event curve showed significantly earlier cumulative normalization time for the intervention group. Conclusion: Single-dose 100 mg methotrexate injection is a low-cost, simple intervention to help one out of three women with CHM with high-risk features to achieve normalization of ßHCG within 56 days. This might be helpful for people in resource-poor countries where adherence to prolonged surveillance is poor.

A Rare Case of Intracavitary Cardiac Metastasis of Endometrial Carcinosarcoma.

A 59-year-old female, with past medical history including endometrial carcinosarcoma with a port-a-cath device, presented due to shortness of breath. Transesophageal echocardiogram demonstrated a mass extending from the right atrium, involving the tricuspid valve, and extending into the right ventricle. Our differential diagnosis included thrombus as well as endocarditis and malignancy; a thrombus was considered to be the most likely etiology due to the port-a-cath device. Use of the novel AngioVac mechanical aspiration device (AngioDynamics, 2021) allowed removal of the mass as well as evaluation by pathology, establishing the unlikely diagnosis of metastatic endometrial carcinosarcoma.

Interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma.

BACKGROUND: The accurate pathologic diagnosis and subtyping of high-grade endometrial carcinoma are often problematic, due to its atypical and overlapping histopathological features. METHODS: Three pathologists reviewed 21 surgically resected cases of advancedstage endometrial carcinoma. The primary diagnosis was based only on hematoxylin and eosin stained slides. When a discrepancy arose, a secondary diagnosis was made by additional review of immunohistochemical (IHC) stains. Finally, three pathologists discussed all cases and rendered a consensus diagnosis. RESULTS: The primary diagnoses were identical in 13/21 cases (62%). The secondary diagnosis based on the addition of IHC results was concordant in four of eight discrepant cases. Among four cases with discrepancies occurring in this step, two cases subsequently reached a consensus diagnosis after a thorough discussion between three reviewers. Next-generation sequencing (NGS) study was performed in two cases in which it was difficult to distinguish between serous carcinoma and endometrioid carcinoma. Based on the sequencing results, a final diagnosis of serous carcinoma was rendered. The overall kappa for concordance between the original and consensus diagnosis was 0.566 (moderate agreement). CONCLUSIONS: We investigated stepwise changes in interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma. We demonstrated the utility of IHC and NGS study results in the histopathological diagnosis of advanced-stage endometrial carcinoma.

Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification.

Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives.

Postoperative Radiotherapy for Endometrial Cancer in Elderly (≥80 Years) Patients: Oncologic Outcomes, Toxicity, and Validation of Prognostic Scores.

Endometrial cancer is a common malignancy in elderly women that are more likely to suffer from limiting medical comorbidities. Given this narrower therapeutic ratio, we aimed to assess the oncologic outcomes and toxicity in the adjuvant setting. Out of a cohort of 975 women, seventy patients aged ≥ 80 years, treated with curative postoperative radiotherapy (RT) for endometrial cancer between 2005 and 2021, were identified. Outcomes were assessed using Kaplan-Meier-analysis and comorbidities using the Charlson Comorbidity Index and G8 geriatric score. The overall survival at 1-, 2- and 5-years was 94.4%, 82.6%, and 67.6%, respectively, with significant correlation to G8 score. At 1- and 5-years, the local control rates were 89.5% and 89.5% and distant control rates were 86.3% and 66.9%, respectively. Severe (≥grade 3) acute toxicity was rare with gastrointestinal (2.9%), genitourinary (1.4%), and vaginal disorders (1.4%). Univariate analysis significantly revealed inferior overall survival with lower RT dose, G8 score, hemoglobin levels and obesity, while higher grading, lymphangiosis, RT dose decrease and the omission of chemotherapy reduced distant control. Despite older age and additional comorbidities, elderly patients tolerated curative treatment well. The vast majority completed treatment as planned with very low rates of acute severe side-effects. RT offers durable local control; however, late distant failure remains an issue.