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Cotyledonoid-dissecting leiomyoma, a very unusual form of uterine leiomyoma, often leads to misdiagnosis as a malignant tumor. Here, we describe a case of a 45-year-old nulliparous woman who underwent a laparoscopic biopsy of a large pelvic mass consisting of multiple flaps. Histologically, the mass was composed of smooth muscle fascicle nodules separated by hydropic connective tissue, and exhibited extensive stromal hyalinization. The tumor was diagnosed as a cotyledonoid-dissecting leiomyoma based on the laparoscopic, pathological, and image findings. Prior to performing radical laparotomy, two courses of leuprorelin were administered in anticipation of tumor reduction and hypoperfusion, and the tumor size reduced remarkably. We demonstrated the utility of laparoscopic biopsy, considering its minimal invasiveness and diagnostic accuracy. Furthermore, the preoperative use of Gonadotropin-releasing hormone (GnRH) analogs to reduce surgical stress may be useful for treating cotyledonoid-dissecting leiomyomas. [ABSTRACT FROM AUTHOR]

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate net survival, cure fraction, time to cure (when 5-year conditional net survival becomes > 95%), cure prevalence (women who will not die of cancer), and already cured (living longer than time to cure). In 2018, 0.4% (121 704) of Italian women were alive after diagnosis of corpus uteri cancer, 0.2% (52 551) after cervical cancer, and 0.2% (52 153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (cure prevalence). Women with gynecological cancers have a residual excess risk of death <5% at 5 years after diagnosis. The cure fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time to cure was ≤10 years for women with gynecological cancers aged <55 years; 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were already cured. These results can contribute to improving follow-up programs for women with gynecological cancers and supporting efforts against discrimination of already cured ones. This article is part of a Special Collection on Gynecological Cancers. [ABSTRACT FROM AUTHOR]

We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that "endometrioid carcinoma with yolk sac tumor differentiation" or "endometrioid carcinoma with a primitive phenotype" may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium. [ABSTRACT FROM AUTHOR]

Background: Primary uterine alveolar soft part sarcoma (ASPS) is a rare, indolent mesenchymal malignancy with less than 40 patients documented in the literature. Case: We report an example of ASPS in a 61-year-old postmenopausal woman. Macroscopically, the uterus showed multiple nodular masses. Microscopic examination revealed tumor arranged in nests and alveolar pattern. The tumor cells were moderately to markedly pleomorphic, epithelioid to polygonal, with eccentrically placed nuclei, vesicular chromatin, prominent macro-nucleoli, and moderate to abundant eosinophilic cytoplasm. PAS-positive and diastase-resistant intracytoplasmic crystals were also seen in some tumor cells. On immunohistochemistry, the tumor cells showed diffuse positivity for vimentin and nuclear positivity for TFE3, a surrogate marker for ASPS. These were negative for SMA, desmin, CD10, h-caldesmon, cyclin D1, EMA, Melan A, and CD34. SMARCB1 expression was retained. Based on the histopathology and IHC, a final diagnosis of uterine ASPS was rendered. Conclusions: Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare tumors. Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare sarcoma in an uncommon site with an unusual age. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is one of the main treatments for cervical cancer. Long-term complications of radiation exposure include the emergence of secondary tumors. This is a retrospective study based on an American population. We discuss the optimal treatment modality for patients with radiation-induced secondary uterine malignancy based on the Surveillance, Epidemiology, and End Results database. Methods: The study included patients with a definitive pathological diagnosis of cervical cancer who were diagnosed with a uterine malignant tumor ≥ 1 year later. Patients in whom cervical cancer was not the first tumor or patients with missing data were excluded. Univariate and multivariate analyses were performed using the COX regression model to screen independent prognostic factors affecting overall survival. Kaplan-Meier survival curves were analyzed using the R software package. Results: We screened 142 patients with a secondary uterine malignancy after cervical cancer treatment, 115 patients with a secondary uterine malignancy after radiotherapy, and 27 patients with a secondary uterine malignancy who did not receive radiotherapy. The average latency period for developing a secondary tumor was 8 years, and 57.04% of the patients had a second tumor at ≥ 60 years of age. In patients with a secondary uterine malignancy after radiotherapy, surgery improved the prognosis [hazard ratio (HR), 0.374; 95% confidence interval (CI), 0.229–0.612], whereas radiotherapy and chemotherapy did not reduce the risk of death. In the subgroup analysis, the surgery plus chemotherapy group had a significantly better survival prognosis than the other groups (HR, 0.251; 95% CI, 0.122–0.515). Conclusions: The results suggest that the treatment modality in patients with secondary uterine malignancy after radiotherapy for cervical cancer has a significant impact on survival. The survival outcomes of patients receiving surgery combined with chemotherapy are superior to those of patients receiving other treatments. [ABSTRACT FROM AUTHOR]

Background: Women with gynecologic disorders requiring a hysterectomy often have co-existing psychiatric diagnoses. A change in the dispensing pattern of antidepressant (AD) and antianxiety (AA) medications around the time of hysterectomy may be due to improvement in gynecologic symptoms, such as pelvic pain and abnormal bleeding, or the emotional impact of the hysterectomy. Unfortunately, these dispensing patterns before and after hysterectomy are currently undescribed. Objectives: To model the dispensing patterns of AD and AA medications over time among women with psychiatric disorders before and after benign hysterectomy for endometriosis and uterine fibroids; and to characterize clusters of patients with various dispensing behaviors based on these patterns. Design: Retrospective cohort study. Methods: This is a study of women who underwent a benign hysterectomy using data from the Merative MarkertScan® Research Databases (Ann Arbor, MI, USA). Inclusion criteria were reproductive-aged women (18–50 years), diagnosis of at least one mood or anxiety disorder, and at least one dispensing of AD or AA medications. We measured monthly adherence and persistence of AD/AA medication use over 12 months after hysterectomy. Group-based-trajectory modeling (GBTM) was used to identify trajectory groups of monthly AD/AA medication dispensing over the study period. Multinomial logistic regression was used to identify factors independently associated with individual dispensing trajectory patterns. Results: For a total of 11,607 patients, 6 dispensing trajectory groups were identified during the study period: continuously high (27.0%), continuously moderate (21.9%), continuously low (17.9%), low-to-high (10.0%), moderate-to-low (9.8%), and low-to-moderate (13.4%). Compared with the continuously high group, younger age, no history of a mood disorder, and uterine fibroids were clinical predictors of low dispensing. The discontinuation rate at 3 months after hysterectomy was higher at 88.6% in the continuously low group and at 66.5% in the continuously low-to-moderate group. Conclusions: This study demonstrates that GBTM identified six distinct trajectories of AD/AA medication dispensing in the perioperative period. Trajectory models could be used to identify specific dispensing patterns for targeting interventions. Plain language summary: Dispensing patterns of antidepressant and antianxiety medications for psychiatric disorders after benign hysterectomy in reproductive-aged women: Results from the group-based trajectory modeling Women with gynecologic disorders often have coexisting psychiatric diagnoses. A change in the dispensing pattern of antidepressant and antianxiety medications may be due to improvement in gynecologic symptoms or the emotional impact of the hysterectomy. However, static measures, such as the proportion of days covered or medication possession ratio, may not adequately predict meaningful dispensing patterns. Using the group-based trajectory modeling, 6 distinct patterns of medication dispensing over the perioperative periods of women with benign hysterectomy are identified and therefore used to assess how certain clinical characteristics influence these dispensing patterns. This study concludes that trajectory modeling may be a more appropriate approach to investigating dispensing patterns among women with preexisting psychiatric conditions. [ABSTRACT FROM AUTHOR]

Few studies have evaluated cytokeratin's (CK) staining patterns in atypical endometrial hyperplasia (AEH) coexisting with early-stage endometrial cancer (EC). We aimed to assess the staining patterns of selected CKs (CK7, CK19, CK20, CK AE1/AE3) in 74 patients with coexisting AEH and EC by independently analyzing both morphological variables. Specimens were collected from women with AEH and EC who underwent surgical interventions between 2012 and 2019 at the Department of Obstetrics and Gynecology of Vilnius University Hospital "Santaros Klinikos" in Vilnius, Lithuania. Immunostaining was also qualitatively classified as being heterogeneous or intense. The results revealed heterogeneous CK7 expression in all AEH cases and intense staining in 95.95% cases of AEH. The heterogeneous expression of CK7 was detected in all EC specimens. Intense CK7 expression was observed in 95.09% cases of EC G1 and in all G2 ECs. Heterogenous CK19 expression was present in all AEH specimens with intense staining in 92.42% of cases. Heterogeneous CK19 expression was observed in all EC samples with intense expression in 86.27% cases of EC G1 and 100% cases of EC G2. Interestingly, a significant relationship was found when comparing the heterogeneous expression of CK19 between AEH and well-differentiated EC. A significant difference was reported in the intense expression of CK AE1/AE3 (p = 0.031; p = 0.029) between AEH and G2 ECs and in the intense expression of CK AE1/AE3 between G1 and G2 ECs. CK20 staining was not a characteristic feature for AEH and early-stage EC. CK staining is present either in AEH or in early-stage endometrioid-subtype EC in different manners. Heterogeneous CK19 expression was significantly more common in AEH than in EC. CK20 expression was not associated with either AEH nor early-stage EC. An intense expression of CK AE1/AE3 was mainly present in moderately differentiated ECs, whereas the intense reactivity of AE1/AE3 showed a significant difference in well to moderately differentiated uterine tumors. The clinical implication of CK staining may aid in the more accurate diagnosis of AEH and early-stage EC as well as detect micrometastases leading to better oncological outcomes. [ABSTRACT FROM AUTHOR]

A captive marmoset developed metastatic endometrioid carcinoma (EnC), a rare uterine tumor in non‐human primates (NHPs). The neoplasm showed marked microscopical malignant and tubulopapillary aspects, immunopositivity for pan‐cytokeratin, CK7, estrogen receptor, and a high mitotic index (Ki‐67). These features may contribute to the diagnosis and therapeutics of EnC in NHPs. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV‐associated cervical lesions is HPV genotype‐dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high‐risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high‐risk HPVs, HPV18 has some peculiar characteristics different from those of other high‐risk HPV types; the detection rate in precancerous lesions is much lower than those of other high‐risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell‐like cells. In this context, this review outlines the natural history of HPV‐infected cervical lesions and the characteristics of each HPV genotype. [ABSTRACT FROM AUTHOR]

Simple Summary: Persistent survival disparities by racial/ethnic groups are expected to worsen with rising incidence rates of aggressive uterine cancer subtypes. Understanding the impact of area-based socioeconomic factors on survival outcomes may help to better understand these disparities. This research aims to understand how living in counties with lower educational attainment, higher poverty, higher unemployment, lower median household income, and population density in urban areas may impact survival rates of women diagnosed with uterine cancer across racial/ethnic groups. Our findings show that lower county-level socioeconomic characteristics are linked with worse survival rates, mainly impacting women diagnosed with aggressive histologic subtypes and underrepresented racial/ethnic groups. Regardless of tumor and socioeconomic characteristics, non-Hispanic (NH) Black women consistently experience the poorest survival outcomes compared to other racial/ethnic groups included in this study. Racial/ethnic disparities in survival were observed even in the most affluent counties, suggesting that other factors beyond county-level socioeconomic status are at play. Understanding socioeconomic factors contributing to uterine cancer survival disparities is crucial, especially given the increasing incidence of uterine cancer, which disproportionately impacts racial/ethnic groups. We investigated the impact of county-level socioeconomic factors on five-year survival rates of uterine cancer overall and by histology across race/ethnicity. We included 333,013 women aged ≥ 30 years with microscopically confirmed uterine cancers (2000–2018) from the Surveillance, Epidemiology, and End Results 22 database followed through 2019. Age-standardized five-year relative survival rates were compared within race/ethnicity and histology, examining the differences across tertiles of county-level percent (%)

Ewing sarcoma is an uncommon neoplasm considered in the differential diagnosis of tumors with "small round cell" morphology, but its occurrence in the gynecologic tract has only been sporadically documented. Herein, we describe the largest cohort of Ewing sarcoma localized to the female genital tract to date, and emphasize their clinicopathologic resemblance to more common gynecologic neoplasms. Ewing sarcoma (n= 21) was retrospectively identified from 5 institutions. The average patient age was 35 (range 6-61) years. Tumor sites included uterus (n= 8), cervix (n=4), vulva (n= 5), vagina (n= 1), broad ligament (n=1), inguinal area (n =1), and pelvis (n= 1). Nine of 18 cases in which slides were available for review demonstrated only classic round cell morphology, with the remainder showing a variable combination and prominence of variant ovoid/spindle or epithelioid appearance. Tumors showed diffuse membranous reactivity for CD99 (20/20) and were positive for NKX2.2 (8/8, diffuse) and cyclin D1 (7/7, of which 3/7 were patchy/multifocal and 4/7 were diffuse). They were negative for ER (0/6) and CD10 (0/6). Three cases were initially diagnosed as endometrial stromal sarcomas. EWSR1 rearrangement was confirmed in 20/21 by fluorescence in situ hybridization (n=15) and/or sequencing (n= 8). Of the eight tumors that underwent sequencing, 6 harbored FLI1, 1 ERG, and 1 FEV as the fusion partner. Of 11 patients with available follow-up, 5 died of disease, 1 developed lung metastases and 5 are alive with no evidence of disease. Ewing sarcoma of the gynecologic tract is a rare, aggressive entity that shares some morphologic and immunohistochemical features with other more common gynecologic neoplasms. In addition to the typical round cell appearance, variant spindled/ovoid to epithelioid morphology may also be observed and should prompt consideration of this entity with appropriate immunohistochemical and/or molecular studies. [ABSTRACT FROM AUTHOR]

Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n= 17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE-mutated (POLEmut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS (P= 0.008) and P=0.0001). POLEmut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication. [ABSTRACT FROM AUTHOR]

Simple Summary: This study compares the survival and surgical outcomes of patients who underwent conventional versus robot-assisted laparoscopy for aggressive histologic types of uterine cancer. While there is no association between the use of robotic assistance and overall survival, robot-assisted laparoscopy is associated with a decreased risk for conversion to laparotomy and a higher rate of surgical lymph node evaluation. The objective of this study is to compare the overall survival (OS) and surgical outcomes between conventional laparoscopy and robot-assisted laparoscopy (RAL) in women with type II endometrial cancer. We identified a large cohort of women who underwent hysterectomy for type II endometrial cancer between January 2010 and December 2014 using the National Cancer Database (NCDB). The primary outcome was to compare the OS of conventional laparoscopy versus RAL. Secondary outcomes included the length of hospital stay, 30-day readmission rate, 90-day mortality, rates of lymph node retrieval, rates of node positivity, and rates of conversion to laparotomy. Cohorts were compared and multivariable logistic regression was used to determine characteristics with statistically significant predictors of outcome. We identified 7168 patients with stage I–III type II endometrial cancer who had minimally invasive surgery as primary treatment between 2010 and 2014. A total of 5074 patients underwent RAL. Women who underwent RAL were less likely to have stage III disease (26.4% vs. 29.9%, p = 0.008) and had smaller primary tumors (4.6 vs. 4.1 cm, p < 0.001). In a multivariable model, there was no difference in OS between conventional laparoscopy and RAL. With regard to postoperative outcomes, RAL was associated with a decreased risk for conversion to laparotomy (2.7% vs. 12%, p < 0.001), a shorter hospital stay (1 vs. 2 days, p < 0.001), a decreased 90-day mortality (1.3% vs. 2.2%, p = 0.004), and an increased number of lymph nodes sampled (14 vs. 12, p < 0.001). In multivariable analysis, the use of RAL was independently associated with a reduced rate of conversion to laparotomy. In conclusion, there was no difference in OS between conventional laparoscopy and RAL in type II endometrial cancer in a large retrospective cohort of patients from the NCDB. RAL was associated with a decreased risk of conversion to laparotomy. [ABSTRACT FROM AUTHOR]

Background: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. Case presentation: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. Conclusions: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS. [ABSTRACT FROM AUTHOR]

Multivariate logistic regression models were used to assess the adjusted relationship between uterine fibroids and BV. Of the 189 patients with uterine fibroids, individuals with BV were more likely to have a submucosal fibroid(s) as compared to those without BV (28.3% vs 10.5%, P = 0.003). The odds of a subsequent diagnosis of BV were higher among patients with submucosal fibroids as compared to those with fibroids in other locations (Odds Ratio: 3.0, 95% CI: 1.3–7.1). Patients with BV demonstrated higher likelihoods of abnormal uterine bleeding (65.5% vs 26.3%, P < 0.001) and anemia (52.2% vs 30.3%, P = 0.003). [ABSTRACT FROM AUTHOR]

Uterine fibroids are the most common gynaecological tumour in women of reproductive age and can cause heavy menstrual bleeding, anaemia, pelvic pain, bowel and bladder dysfunction, and infertility. While treatment options can be pharmacological, procedural or surgical, an individualized management approach is recommended. The choice of treatment depends on several factors, including the woman's age, symptoms, preferences and reproductive goals, and the location, number and size of the fibroids. Pharmacological therapies often aim to manage heavy menstrual bleeding or bulk symptoms, with the hormonal dependence of uterine fibroids the mechanism by which most of them act. [ABSTRACT FROM AUTHOR]

Introduction: Gestational trophoblastic neoplasia (GTN) is a malignant form of gestational trophoblastic diseases originating from abnormal proliferation of placental trophoblasts. Owing to unusual and variable presentations, the diagnosis is sometimes delayed and become catastrophic. Though, survival outcomes are good following chemotherapy, but still surgery becomes first choice in hemodynamically unstable patient which is to be followed by chemotherapy depending upon the World Health Organization (WHO) prognostic score. The reproductive outcomes following chemotherapy is variable. Here, we are reporting a case series of GTN with varied presentation giving different lessons which were managed to best of our possible efforts. Case discussion: The first case highlights the management of women who had ruptured choriocarcinoma post manual vaginal examination for which hysterectomy was performed as a life-saving procedure followed by chemotherapy. The other case surprised the clinician with metastatic perforating invasive mole along with unusual finding of ovarian and iliac vein thrombosis. Although, planned for chemotherapy, hysterectomy with debulking was done for hemoperitoneum. The last case perplexed us with the normal twin conception just following the completion of chemotherapy for post-molar high-risk GTN and is continuing her viable pregnancy. Conclusion and clinical implication: Our case series imparted few lessons to obstetricians. Pelvic examination in GTN needs to be guarded so as to prevent untoward life-threatening complications. Invasive mole may present lately with devastating rupture uterus with exuberant pelvic vein thrombosis (PVT). Spontaneous conception with good reproductive outcome may still occur immediately following completion of multi-agent chemotherapy in high-risk GTN. [ABSTRACT FROM AUTHOR]

Objective: As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. Methods: This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. Results: After a median follow-up of 137.0 months (95% confidence interval=85.4-188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). Conclusions: The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended. [ABSTRACT FROM AUTHOR]

Fibroids are benign uterine tumors characterized by the proliferation of uterine smooth muscle cells, embedded in an abundant extracellular matrix. Their prevalence is estimated to be >50% in women aged >45 years. Fibroids represent a considerable health burden. It is time to acquire a deeper mechanistic understanding of uterine fibroid-related etiology and pathogenesis, which may help pinpoint new strategies and an individualized approach. There is a need to gather prospective data and conduct studies to compare alternative approaches and assess long-term outcomes with respect to quality of life, recurrence of symptoms (bleeding and bulk symptoms), fertility, and even complications The goal of this review was to evaluate the widely accepted pathogenesis and identify risks factors and future directions for clinical and basic research into fibroids. [ABSTRACT FROM AUTHOR]

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Background Uterine leiomyosarcoma (uLMS) represents one of the most common sarcoma histotypes, demonstrating an overall dismal prognosis. Previous studies reported uLMS to carry recurrent somatic BRCA2 homozygous deletions, related to significant clinical benefits from the use of PARP inhibitors. Methods To investigate the prevalence in uLMS of genomic alterations (alt) in BRCA2 and other homologous recombination (HR) and DNA damage response (DDR) genes, cBioPortal was accessed and data were retrieved from studies including pan-sarcoma histologies. HR-/DDR-genes included BRCA1 , BRCA2 , ATM , BARD1 , BRIP1 , CHEK1 , CHEK2 , FANCA , FANCB , FANCC , FANCD2 , FANCE , FANCF , FANCG , FANCI , FANCL , FANCM , NBN , PALB2 , RAD51C , RAD51D , RAD50 , and ATR. Only oncogenic/likely oncogenic alterations were included according to OncoKB. Clinical Report and Results We reported a clinical case of a patient affected by a highly pretreated uLMS discussed at the European Institute of Oncology Molecular Tumor Board. A targeted next-generation sequencing panel demonstrated a somatic BRCA2 homozygous deletion (homDel). Upon access to Niraparib, a remarkable response of 15 months was observed before experiencing disease progression. In the genomic query, among 2393 cases, uLMS (n  = 193) displayed 9 of all 31 BRCA2 alt observed, representing the only sarcoma histotype showing an enrichment in BRCA2 alt (4.66%; q  < 0.001). All of 9 BRCA2 alt were represented by homDel, which related to a high fraction of genome altered. Conclusion uLMS displays a significant frequency of somatic BRCA2 alt homDel. Considering their dismal prognosis, further investigation is warranted to test the use of PARPi in uLMS, and particularly in the setting of BRCA1/2 alterations. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal uterine tumors are a diverse group of neoplasms with varying biological potential. Many of these neoplasms can have overlapping morphologic similarities, which, in some instances, render their diagnosis and categorization thorough histomorphologic examination inconclusive. In the last decade, an exponential amount of molecular data aiming to more accurately characterize and, consequently, treat these tumors have accumulated. Objective: The goal of this narrative review is to provide a pathologic review, a genetic update, and to know the new therapeutic avenues of primary uterine mesenchymal neoplasms. [ABSTRACT FROM AUTHOR]

Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers. We collected clinical data and formalin‐fixed paraffin‐embedded (FFPE) samples for analysis at the DNA level using panel‐based next‐generation sequencing and array‐comparative genomic hybridization. Additionally, we examined mRNA expression using NanoString nCounter® and protein expression through tissue microarray. We compared EOvC with other ovarian subtypes and uterine endometrioid tumors. Furthermore, we assessed the impact of molecular alterations on patient outcomes, including progression‐free survival (PFS) and overall survival (OS). Preliminary analysis of clinical data from 668 patients, including 86 (12.9%) EOvC, revealed more favorable prognosis for EOvC compared with serous ovarian carcinoma (5‐year OS of 60% versus 45%; P = 0.001) driven by diagnosis at an earlier stage. Immunohistochemistry and copy number alteration (CNA) profiles of 43 cases with clinical data and FFPE samples available indicated that EOvC protein expression and CNA profiles were more similar to endometrioid endometrial tumors than to serous ovarian carcinomas. EOvC exhibited specific alterations, such as lower rates of PTEN loss, mutations in DNA repair genes, and P53 abnormalities. Survival analysis showed that patients with tumors harboring loss of PTEN expression had worse outcomes (median PFS 19.6 months vs. not reached; P = 0.034). Gene expression profile analysis confirmed that EOvC differed from serous tumors. However, comparison to other rare subtypes of ovarian cancer suggested that the EOvC transcriptomic profile was close to that of ovarian clear cell carcinoma. Downregulation of genes involved in the PI3K pathway and DNA methylation was observed in EOvC. In conclusion, EOvC represents a distinct biological entity and should be regarded as such in the development of specific clinical approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Uterine leiomyosarcoma (uLMS) is a rare and aggressive malignancy with treatments that have limited efficacy and often have significant toxicities. We previously demonstrated the presence of Notch signaling in uLMS as well as decreased cell viability and Notch expression after exposure to the gamma secretase inhibitor MK-0752. The aim of this study was to assess the combination of MK-0752 and chemotherapeutics commonly used for the treatment of uLMS. Using two human uLMS cell lines, SK-UT-1B and SK-LMS-1, we demonstrated synergism between MK-0752 and docetaxel, doxorubicin, and gemcitabine using MTT assays. These synergistic combinations were used in transwell invasion assays, cell cycle flow cytometry, proliferation assays, and RNA sequencing. We found decreased invasion, an increase in the apoptotic sub-G1 cell cycle population, and differentially expressed genes and altered KEGG pathways after combination treatment. The combinations of MK-0752 and doxorubicin, MK-0752 and docetaxel, and MK-0752 with gemcitabine and docetaxel are potential novel therapeutic approaches for uLMS. Due to limited effective therapeutics for uterine leiomyosarcoma (uLMS), the impact of the gamma secretase inhibitor (GSI) MK-0752 with common chemotherapeutics was explored in uLMS. MTT assays were performed on two human uLMS cell lines, SK-UT-1B and SK-LMS-1, using MK-0752, docetaxel, doxorubicin, and gemcitabine, individually and in combination, to determine cell viability after treatment. Synergistic combinations were used in transwell invasion assays, cell cycle flow cytometry, proliferation assays, and RNA sequencing. In SK-UT-1B, MK-0752 was synergistic with doxorubicin and gemcitabine plus docetaxel. In SK-LMS-1, MK-0752 was synergistic with all individual agents and with the combination of gemcitabine plus docetaxel. MK-0752, gemcitabine, and docetaxel decreased invasion in SK-UT-1B 2.1-fold* and in SK-LMS-1 1.7-fold*. In SK-LMS-1, invasion decreased 1.2-fold* after treatment with MK-0752 and docetaxel and 2.2-fold* after treatment with MK-0752 and doxorubicin. Cell cycle analysis demonstrated increases in the apoptotic sub-G1 population with MK-0752 alone in SK-UT-1B (1.4-fold*) and SK-LMS-1 (2.7-fold**), along with increases with all combinations in both cell lines. The combination treatments had limited effects on proliferation, while MK-0752 alone decreased proliferation in SK-LMS-1 (0.63-fold**). Both MK-0752 alone and in combination altered gene expression and KEGG pathways. In conclusion, the combinations of MK-0752 with either doxorubicin, docetaxel, or gemcitabine plus docetaxel are potential novel therapeutic approaches for uLMS. (* p < 0.05, ** p < 0.01). [ABSTRACT FROM AUTHOR]

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare form of uterine mesenchymal neoplasm. Although UTROSCT generally exhibits benign behavior with a favorable prognosis, this neoplasm is nevertheless classified as being of uncertain malignant potential, given its low rate of recurrence and the fact that it rarely produces metastases (e.g., in the lymph nodes, epiploic appendix, omentum, small bowel, subcutaneous tissue, lungs). Its histogenesis is also uncertain. Typically, UTROSCT occurs in peri-menopausal or menopausal women, but it can sometimes be observed in young women. Usually, this neoplasm can be found in the uterine corpus as a nodular intramural lesion, while it is less frequently submucosal, subserosal, or polypoid/intracavitary. UTROSCT can cause abnormal bleeding, pelvic pain, enlarged uterus, and mass sensation, but sometimes it is found purely by chance. This neoplasm can be considered polyphenotypic on morphological, immunohistochemical, and genetic analyses. Generally, upon microscopic examination, UTROSCT shows a predominant pattern of the cords, nests, and trabeculae typical of sex-cord tumors of the ovary, while immunohistochemically it is characterized by a coexpression of epithelial, smooth muscle, and sex-cord markers. The aim of this review is to report clinical and pathological data and genetic alterations to establish their impact on the prognosis and management of patients affected by this rare entity. [ABSTRACT FROM AUTHOR]

Cyclic volatile methyl siloxanes (cVMS) have now become a subject of environmental contamination and risk assessment due to their widespread use and occurrence in different environmental matrices. Due to their exceptional physio-chemical properties, these compounds are diversely used for formulations of consumer products and others implying their continuous and significant release to environmental compartments. This has captured the major attention of the concerned communities on the grounds of potential health hazards to human and biota. The present study aims at comprehensively reviewing its occurrence in air, water, soil, sediments, sludge, dusts, biogas, biosolids, and biota and their environmental behavior as well. Concentrations of cVMS in indoor air and biosolids were higher; however, no significant concentrations were observed in water, soil, and sediments except for wastewaters. No threat to the aquatic organisms has been identified as their concentrations do not exceed the NOEC (maximum no observed effect concentration) thresholds. Mammalian (rodents) toxicity hazards were not very evident except for the occurrence of uterine tumors in very rare cases under long-term chronic and repeated dose exposures in laboratory conditions. Human relevancy to rodents were also not strongly enough established. Therefore, more careful examinations are required to develop stringent weight of evidences in scientific domain and ease the policy making with respect to their production and use so as to combat any environmental consequences. [ABSTRACT FROM AUTHOR]

Objective: To estimate the incidence and report the details of hystological, clinical, surgical, and demographic features of incidental uterine sarcomas in patients operated with symptomatic myoma uteri. Material and Methods: We designed a retrospective cohort study at Adnan Menderes University Gynecologic Oncology Department that includes totally 896 patients with symptomatic myoma uteri who were operated as a hysterectomy or myomectomy. Following the definition of inclusion and exlusion criterias, incidental uterine sarcoma cases were detailed as histological subtype, tumor diameter, morcellation or fragmentation status in surgery, adjuvant treatment, recurrences, and survival. All cases were reported as a table without specific statistical analyzes. Results: A total of 775 hysterectomy and 121 myomectomy cases were analyzed. Fourteen sarcoma cases were reported. Two sarcoma cases were excluded due to adnexal sarcoma in final pathology. Ten cases were reported in final pathology incidentally. 7/10 cases were reported as leiomyosarcoma while low grade endometrial stromal sarcoma were reported in 2 cases. While all recurrences were seen in leiomyosarcoma group (5 cases), two of them died with disease-related complications. Conclusion: Studies have shown that uterine sarcomas are malignancies that are extremely rare and cannot be predicted preoperatively. Due to its low incidence and uncertain tumor behavior, in low-risk patients, myomectomy with mechanical or power morcellation is a safe surgical option when it is perfomed without abdominal spillage which can be common in laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Sentinel lymph node (SLN) mapping for the surgical staging of endometrial and cervical cancer is commonly performed by laparoscopy, but recently, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery approach has been described and developed by Jan Baekelandt. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLN assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is in Stage 2a, with only small case series as evidence of its feasibility. Provided that the standardized description of this surgical technique appears necessary to provide the homogeneity required to move further in its investigation, here, we describe a 10-step approach for performing it successfully. This could help other surgeons approach this new technique, and it proposes a common methodology necessary for evolving through future studies. (1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described and developed by Jan Baekelandt. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLN assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is in Stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: Description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: We describe a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL Stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary for evolving through future IDEAL Stage 2b (multi-center studies) and Stage 3 (randomized controlled trials) studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer has emerged as the main gynecological malignant tumour in developed countries. The development of molecular techniques allows the precise profiling of each case. This affects the selection of a therapy and the patient's prognosis. Long non-coding RNAs, which influence tumour development, are a novelty in endometrial cancer. They can both stimulate and inhibit the progression of the disease. Their number is constantly growing, and the mechanisms of action are not fully discovered. Some of them may become targets for new molecular therapies in the future. Endometrial cancer is one of the most common malignant tumours in women. The development of this tumour is associated with several genetic disorders, many of which are still unknown. One type of RNA molecules currently being intensively studied in many types of cancer are long non-coding RNAs (lncRNAs). LncRNA-coding genes occupy a large fraction of the human genome. LncRNAs regulate many aspects of cell development, metabolism, and other physiological processes. Diverse types of lncRNA can function as a tumour suppressor or an oncogene that can alter migration, invasion, cell proliferation, apoptosis, and immune system response. Recent studies suggest that selected lncRNAs are important in an endometrial cancer course. Our article describes over 70 lncRNAs involved in the development of endometrial cancer, which were studied via in vivo and in vitro research. It was proved that lncRNAs could both promote and inhibit the development of endometrial cancer. In the future, lncRNAs may become an important therapeutic target. The aim of this study is to review the role of lncRNAs in the development of carcinoma of uterine body. [ABSTRACT FROM AUTHOR]

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given. [ABSTRACT FROM AUTHOR]

Background: B-Lynch braided compression sutures are applied as a lifesaving procedure to control atonic post-partum hemorrhage if the patient is not responding to uterotonics and other conservative methods. These sutures are applied to avoid hysterectomy so as to preserve fertility. However, if not applied properly, these can lead to a rare but serious complication of uterine necrosis secondary to uterine ischemia and sepsis. The patient then ends up in hysterectomy defeating the sole purpose of maintaining fertility for which the sutures were applied at the first place. Case presentation: Here we describe a case of primipara who had caesarian section complicated by post-partum hemorrhage which was managed with modified B-Lynch compression sutures for achieving hemostasis. The patient presented three weeks post-procedure with signs and symptoms of inflammation and sepsis. The MR imaging revealed features of uterine necrosis. The patient underwent hysterectomy unwillingly as no other option was left to save her life. A detailed MR imaging of this case has been described given the scarcity of MR features of uterine necrosis following compressive sutures in medical literature. Conclusions: The case is reported to make the clinicians aware of the possibility of such a dreaded complication following compressive sutures for post-partum hemorrhage and to emphasize on early and timely follow-up of such patients so that uterus could be salvaged. [ABSTRACT FROM AUTHOR]

Simple Summary: The research explores the potential of the Wnt receptor ROR1 as a target for cancer treatment, an area gaining significant attention. Despite ongoing therapeutic investigations, the understanding of ROR1's presence in different tissues remains limited. To address this, the study conducted immunohistochemistry analyses on a large variety of tumor types, including sarcomas and carcinomas, revealing a diverse ROR1 expression pattern. Notably, high ROR1 prevalence was observed in mesothelioma, liposarcoma, gastrointestinal stromal tumors, and uterine endometrioid carcinoma. Conversely, other cancers showed lower expression. These findings highlight the potential for ROR1-targeted therapies, particularly in mesothelioma, which exhibits frequent and high ROR1 expression, suggesting a novel therapeutic avenue. This research may inform the development of more effective cancer treatments targeting ROR1. The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake. Primary Aim: Assess cervical cancer screening rates over time, particularly primary HPV test uptake, among patients in a midwestern practice. Secondary Aim: Evaluate associations between sociodemographics and screening adherence. Methods: Cross-sectional study. Qualifying subjects and type of screening test used were identified by applying ICD-9, ICD-10, lab test, and CPT codes to the Unified Data Platform. Sociodemographics were found through the electronic health record. Results: Primary HPV uptake represented <1% of annual screening from 1/2017 to 1/2022. On 1/1/2022, only 55% of 21 to 29 year old and 63% of 30 to 65 year old were up to date with screening among the studied population. For 21 to 29 year old, compared with White women, Black women were 28% less likely to be screened [RR = 0.72 (0.66-0.79)]. Compared with never-smokers, current smokers were 9% less likely to be screened [RR = 0.91 (0.87-0.96)], past smokers were 14% more likely [RR = 1.14 (1.09-1.2)]. Among 30 to 65 year old, compared with White women, Black women were 14% less likely to be screened [RR = 0.86 (0.81-0.9)]. Compared with never-smokers, current smokers were 21% less likely to be screened [RR = 0.79 (0.77-0.81)], past smokers were 6% less likely [RR = 0.94 (0.92-0.95)]. Jointly considering race, ethnicity, smoking status, Charlson score, and rurality, findings were similar for 21 to 29 year old; Black women were screened less than White women [RR = 0.73 (0.67-0.79)]; current smokers [RR = 0.9 (0.85-0.94)] and past smokers [RR = 1.12 (1.06-1.17)] were screened less than never smokers. For 30 to 65 year old, Black women were screened less than White women [RR = 0.83 (0.79-0.88)]; current smokers [RR = 0.8 (0.78-0.81)] and past smokers [RR = 0.95 (0.93-0.96)] were screened less than never smokers. Conclusions: Screening rates remained below the Healthy People 2030 goal of 79.2% over time, particularly for younger Black women and current smokers, with minimal use of primary HPV screening. [ABSTRACT FROM AUTHOR]

Objective: To investigate damaging effects of clomifene citrate (CC) on endometrial stromal cells (hEndoSCs), and to study effects of spermidine on autophagy and inflammatory cytokine expression in damaged endometrial stromal cells. Methods: Groups were firstly divided into control group, spermidine group, clomiphene group (CC group), CC+Spermidine group. MTT assay was used to detect cell survival rate of hEndoSCs after co-incubation with different concentrations of CC or Spermidine for 24 h. Content of intracellular reactive oxygen species (ROS) and level of apoptosis in cells of the 4 groups were detected by flow cytometry technique. Western blot was used to detect expressions of autophagy pathway-related proteins ULK1, p-ULK1, LC-3 H, and apoptosis-related proteins Bax, Bcl-2, Cleaved-caspase 3. RT-qPCR was used to detect mRNA expressions of IL-6, IL-1β and TNF-α. Results: Compared with control group, CC group showed decreased cell survival, increased apoptosis rate, ROS content, Bax, Cleaved-caspase 3 expressions, decreased Bcl-2 expression, decreased levels of autophagy-related proteins p-ULK1 and LC-3 II/I, and elevated expressions of inflammatory factors IL-6, IL-1β and TNF-α mRNA (P<0.01). There was no significant changes viability of cells in spermidine group compared with control group (P>0.05). Compared with CC group, cell survival rate in CC+spermidine group was significantly increased, apoptosis rate, ROS content, Bax and Cleaved-caspase 3 expressions were decreased, Bcl-2 expression was increased, expressions of autophagy-related proteins p-ULK1 and LC-3 H/I were elevated, while expressions of inflammatory factors IL-6, IL-1β and TNF-α mRNA were decreased (P<0.01). Conclusion: CC can inhibit endometrial stromal cell proliferation, promote apoptosis, and increase the transcript levels of inflammatory factors IL-6, IL-1β and TNF-α. Spermidine can reduce intracellular ROS in clomiphene-injured endometrial stromal cells by activating cellular autophagy, increase cell survival, and inhibit the expressions of inflammatory factors IL-6, IL-1β and TNF-α. [ABSTRACT FROM AUTHOR]

Stage at diagnosis is one of the key factors determining survival rates of gynaecological cancers. Rapid access pathways were developed in the UK nearly two decades ago, aimed at diagnosing cancers at an earlier stage. Also known as cancer pathways, these consist of standardised referral methods to specialist clinics, where patients undergo diagnostic investigations, receive results and commence treatment swiftly. National cancer waiting time targets exist in conjunction with these pathways and have evolved in recent years to place an emphasis on confirming or excluding cancer within shorter timeframes. In this article we shall consider these UK-based pathways and targets in more detail, along with the challenges hospital trusts face in meeting them. We shall also outline the investigations required to diagnose the four most common gynaecological cancers - uterine, ovarian, cervical and vulval. [ABSTRACT FROM AUTHOR]

Nowadays, the prevalence of uterine myoma in pregnant women has increased due to the increasing age of pregnancy in women. In this case report, a pregnant woman (window period) with a negative result of βhCG test and ultrasound in terms of pregnancy underwent myomectomy surgery to remove a large uterine myoma. A 40-year-old patient referred to the physician because of heavy and prolonged menses caused by a large uterine myoma and primary infertility for 10 years. βhCG test and ultrasound of the patient were negative in terms of pregnancy, and she underwent myomectomy surgery while the patient was in the early stages of pregnancy (window period). Therefore, the patient was under close care during pregnancy. With continuous follow-up, the newborn was born without any problems at 37 weeks. Although in this study, with proper management during surgery, and continuous and regular follow-ups, the newborn was born healthy, but confirmation of myomectomy during pregnancy requires the implementation of more studies. [ABSTRACT FROM AUTHOR]

Uterine fibroids are a common cause of heavy menstrual bleeding and pain. Treatment with the combination of relugolix (an oral gonadotropin-releasing hormonereceptor antagonist), estradiol, and norethindrone acetate, administered once daily, may have efficacy in women with uterine fibroids and heavy bleeding while avoiding hypoestrogenic effects. Methods. We conducted two replicate international, double-blind, 24-week, phase 3 trials involving women with fibroidassociated heavy menstrual bleeding. Participants were randomly assigned in a 1:1:1 ratio to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy end point in each trial was the percentage of participants with a response (volume of menstrual blood loss <80 ml and a ≥50% reduction in volume from baseline) in the relugolix combination therapy group, as compared with the placebo group. Key secondary end points were amenorrhea, volume of menstrual blood loss, distress from bleeding and pelvic discomfort, anemia, pain, fibroid volume, and uterine volume. Safety and bone mineral density were assessed. Result. A total of 388 women in trial L1 and 382 in trial L2 underwent randomization. A total of 73% of the participants in the relugolix combination therapy group in trial L1 and 71% of those in trial L2 had a response (primary end point), as compared with 19% and 15%, respectively, of those in the placebo groups (P<0.001 for both comparisons). Both relugolix combination therapy groups had significant improvements, as compared with the placebo groups, in six of seven key secondary end points, including measures of menstrual blood loss (including amenorrhea), pain, distress from bleeding and pelvic discomfort, anemia, and uterine volume, but not fibroid volume. The incidence of adverse events was similar with relugolix combination therapy and placebo. Bone mineral density was similar with relugolix combination therapy and placebo but decreased with relugolix monotherapy. Conclusions. Once-daily relugolix combination therapy resulted in a significant reduction in menstrual bleeding, as compared with placebo, and preserved bone mineral density in women with uterine fibroids. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To elucidate prognostic factors, determine the best course of treatment methods, and assess oncological results in individuals diagnosed with uterine sarcoma. STUDY DESIGN: Between January 2001 and August 2023, 30 patients with uterine sarcomas (US) were included and analyzed in this cross-sectional study. Sixteen patients (53.3%) had uterine leiomyosarcoma, 6 patients (20%) had high-grade endometrial stromal sarcoma, 8 patients (26.7%) had low-grade endometrial stromal sarcoma. RESULTS: The median follow-up of all participants was 50 months. Recurrence was detected in 43.3% of the patients. 5-year survival ratio was 73.3%, 5-year disease-free survival ratio was 66.7%, the overall survival ratio was 70% and the overall disease-free survival rate was 56.6%. No difference was observed between groups in terms of survival comparisons. No statistically significant effect of adjuvant systemic chemotherapy, adjuvant radiotherapy, and combined treatments on median overall survival and median disease-free survival was detected (p>0.05). CONCLUSION: Uterine sarcomas are uncommon malignancies characterized by a poor prognosis, even in early stages, and they are associated with a high recurrence ratio. The most effective treatment method remains unclear to date. [ABSTRACT FROM AUTHOR]

Background: Black women and people with uteri have utilized collectivistic and relational practices to improve health outcomes in the face of medical racism and discrimination for decades. However, there remains a need for interventions to improve outcomes of uterine fibroids, a condition that disproportionately impacts Black people with uteri. Leveraging personalized approaches alongside evidence that demonstrates the positive impact of social and peer support on health outcomes, we adapted from CenteringPregnancy, an evidence based group prenatal care intervention, for the education and empowerment of patients with uterine fibroids. Methods: The present report provides an overview of the study design and planned implementation of CPWF in cohorts at Boston Medical Center and Emory University / Grady Memorial Hospital. After receiving training from the Centering Healthcare Institute (CHI), we adapted the 10-session CenteringPregnancy curriculum to an 8-session hybrid group intervention called Centering Patients with Fibroids (CPWF). The study began in 2022 with planned recruitment of six cohorts of 10-12 participants at each institution. We will conduct a mixed methods evaluation of the program using validated survey tools and qualitative methods, including focus groups and 1:1 interviews. Discussion: To date, we have successfully recruited 4 cohorts at Boston Medical Center and are actively implementing BMC Cohort 5 and the first cohort at Emory University / Grady Memorial Hospital. Evaluation of the program is forthcoming. Plain English Summary: Fibroids are non-cancerous smooth muscle tumors that disproportionate impact black women and gender expansive people. Our team adapted CenteringPregnancy, a group based model of prenatal care, to an education and empowerment program for peple with fibroids called Centering Patients with Fibroids (CPWF). This paper describes the development and implemation of the program at two academic hospitals serving diverse patients in Boston, Massachusetts and Atlanta, Georgia. To evaluate the successes and challenges of the program, we ask participants to complete surveys to learn more about their experience with having fibroids and also invite them to group feedback sessions or focus groups. We also interview other healthcare providers, team members, and hospital leadership on their knowledge and thoughts about the program. We hope to use the feedback to improve the program and make it available to more people across the country. [ABSTRACT FROM AUTHOR]

There have been no reported cases of neuroendocrine carcinoma (NEC) of the cervix with pagetoid spread (Pag‐S). A 44‐year‐old woman came to our department because of abnormal cytology that persisted immediately after a radical hysterectomy for NEC of the cervix. A mapping biopsy in a large area from the vaginal wall to the vulva revealed that synaptophysin/Ki‐67‐positive tumor cells were scattered within the epithelium in multiple areas, suggesting a wide Pag‐S of NEC. Because tumor cells were found beyond the vaginal wall, the anterior pelvic exenteration was performed. Since we could pathologically confirm the complete resection and no distant metastases were detected, no adjuvant therapy was performed. Four years have passed since the initial treatment without any tumor recurrence. It is known that the prognosis of NEC of the cervix that invades beyond the cervix is poor; however, if there is a Pag‐S pattern, a radical surgical treatment can be considered. [ABSTRACT FROM AUTHOR]

• In total, 147 cases (72 articles) reporting the clinical course of uterine tumours resembling ovarian sex cord tumours (UTROSCTs) were examined. These tumours are extremely rare. • No significant difference in 10-year disease-free survival was found between patients who underwent hysterectomy and patients who underwent mass resection. • Mass resection is an acceptable treatment option in patients aged < 40 years who wish to preserve their childbearing potential. • It is recommended that women who wish to achieve pregnancy should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years based on the low risk of recurrence or metastasis. Uterine tumours resembling ovarian sex cord tumours (UTROSCTs) are extremely rare. To date, most patients with UTROSCTs have undergone hysterectomy and had a benign clinical course. Fertility-preserving surgery should be considered because some patients with UTROSCTs are aged < 40 years. This paper reviews the treatment and prognosis for patients with UTROSCTs, with a focus on fertility. PubMed, MEDLINE and Scopus were searched systematically for case reports and case series of UTROSCTs published in English from inception to December 2022, and initial treatment and recurrence rates were compared. The following data were extracted: age; symptoms; initial therapy; metastasis at diagnosis; disease-free survival (DFS); and recurrence. In total, 147 patients (72 studies) reporting the clinical course of UTROSCTs were analysed. The median age at diagnosis was 50 years, and 28 (19.0 %) patients were aged < 40 years. Most patients (n = 125, 85.0 %) underwent hysterectomy as the initial surgery, with a recurrence rate of 17.6 % (n = 22). The recurrence rate was 30 % (n = 6) in patients who underwent mass resection (n = 20). Among the 15 patients who underwent mass resection aged < 40 years, seven went on to achieve pregnancy (46.7 %) and six had successful deliveries (40.0 %). No significant differences in 5- and 10-year DFS were found between the hysterectomy and mass resection groups (p = 0.123 and 0.0612, respectively). Bilateral salpingo-oophorectomy in addition to hysterectomy was not significantly associated with 10-year DFS (p = 0.548). While total hysterectomy is the recommended treatment for UTROSCTs based on recurrence rates, mass resection is an acceptable treatment option for patients who wish to retain their childbearing potential. It is recommended that these women should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years. [ABSTRACT FROM AUTHOR]

Objectives: This paper aims to comprehensively analyze trends in gynecological cancers among elderly women in the United States from 1975 to 2020. Methods: Surveillance, Epidemiology, and End Results (SEER) population data were utilized for the analysis. Annual Percentage Change (APC) and Average APC were estimated using join‐point regression to assess trends in mortality rates. Results: The study reveals an increasing pattern of incidence and mortality in all gynaecological cancer sites except cervical cancer among elderly. The incidence of cervical cancer decreased from 1975 to 2007 and then increased, whereas cancer‐specific mortality decreased from 1977 to 2020, indicating positive advancements in detection and treatment. Conclusions: Despite progress in managing certain gynecological cancers, challenges persist, particularly evidenced by increasing mortality rates for cancers in other female genital organs. This underscores the necessity for sustained research efforts and targeted interventions to address these ongoing challenges effectively. [ABSTRACT FROM AUTHOR]

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Up to 70–80% of women of reproductive age may be affected with the most common uterine tumors, known as fibroids or myomas. These benign tumors are the second most prevalent cause of surgery among premenopausal women. Predictions show that the occurrence of myomas in pregnancy will increase, and that the risk of having myomas during pregnancy increases with advanced maternal age. Although most women with fibroids do not experience any symptoms during pregnancy, up to 30% of women experience problems during pregnancy, childbirth, and the puerperium. The viability of myoma excision during cesarean surgery (CS) is a contentious issue raised by the rising incidence of myomas in pregnancy and CS rates. A new surgical procedure for removing fibroids using a trans-endometrial approach, which involves making an incision through the decidua itself, has put into doubt the long-standing practice of cesarean myomectomy (CM) with a trans-serosal approach. Some authors have recently advocated for this last approach, highlighting its advantages and potential uses in real-world situations. The purpose of this paper is to critique the present approach to cesarean myomectomy by analyzing the clinical and surgical distinctions between the two approaches and providing illustrations of the CM methods. [ABSTRACT FROM AUTHOR]

Background: Choriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal metastatic involvement by post molar choriocarcinoma is even rarer. In this case report, we describe a unique case of post molar choriocarcinoma with a solitary renal metastasis in the absence of a primary uterine tumor and metastases in other sites, which presented with urological symptoms and spontaneous renal hemorrhage. Case presentation: A 41-year-old Persian woman with history of complete hydatiform mole presented with severe flank pain, nausea, vomiting, gross hematuria, and vaginal bleeding. Laboratory tests demonstrated a serum beta human chorionic gonadotropin hormone level of 60,000 mIU/mL. Imaging studies showed a lesion at the lower pole of the left kidney with active bleeding surrounded by hematoma, as well as an empty uterine cavity. Additionally, bilateral pleural effusion was detected without any lesion within the lungs. Subsequently, the patient underwent laparotomy, partial nephrectomy, and left para-ovarian cystectomy. Endometrial curettage was also carried out. The histopathology report revealed choriocarcinoma renal metastasis with high expression of beta human chorionic gonadotropin, cytokeratin 7, and Ki 67. Moreover, there were no malignant cells in the endometrial curettage specimens, and a corpus luteum cyst was found within the para-ovarian cyst. Further investigations revealed that the pleural effusion was free of malignant cells, and there was no evidence of metastatic lesions in the brain. As a result, the patient was referred to the oncology department to receive chemotherapy, and the beta human chorionic gonadotropin levels dropped to 5 mIU/mL after receiving courses of a standard regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine/oncovin over 3 weeks. Finally, monthly measurements of beta human chorionic gonadotropin levels for 6 months indicated that levels have constantly remained within normal ranges, showing no evidence of recurrence or new metastasis. Conclusions: Urological symptoms such as hematuria or spontaneous renal hemorrhage might be the only presentation of post molar choriocarcinoma with renal involvement. Thus, it can be beneficial to measure serum beta human chorionic gonadotropin levels among females of childbearing age who present with unexplained urological symptoms, especially if there is a history of prior hydatiform mole. [ABSTRACT FROM AUTHOR]

Simple Summary: In situ/microinvasive adenocarcinoma of the uterine cervix represents the majority of cervical glandular lesions and can be treated conservatively. In contrast to squamous lesions, approximately 15–20% of glandular disease may be HPV-negative and therefore associated with a worse prognosis. Furthermore, up to 4% of cases may show recurrence after three years of follow-up. Given the abovementioned risk, knowing the predictive factors of disease recurrence becomes crucial for post-treatment management. In the present study, HPV testing in follow-up was the best predictor for recurrences in women with in situ/microinvasive AC undergoing conservative treatment. So, its use in clinical practice is of pivotal importance. However, attention should be paid to non-high-risk HPV women in follow-up with non-usual-type histopathology, given that it seems to represent a sub-population at increased risk of recurrences. Objective: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Methods: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan–Meier survival analysis with Logrank test were performed. Results: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47–26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). Conclusion: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Uterine leiomyosarcoma is a rare gynecological malignancy, the limited literature indicated that doxorubicin alone or gemcitabine/docetaxel combination is the preferred chemotherapy regimen. Given the rarity of the disease and the lack of high-level clinical evidence, there is no consensus on the best treatment. Case report: We report a case of a patient with uterine leiomyosarcoma who recurred after adjustment treatment with doxorubicin, gemcitabine, docetaxel, and anlotinib; and required a new chemotherapy regimen. Management and outcomes: The follow-up chemotherapy regimen was doxorubicin-liposome 40 mg/m2 on one day in combination with dacarbazine 250 mg/m2 on one to five days of intravenous infusion every 21 days. We monitored adverse effects during chemotherapy and the process was smooth. Discussion: It is important to comprehensively consider the patient's condition, and fully consider the efficacy, dosage, and adverse reactions of the chemotherapy regimen to determine the appropriate plan, in order to achieve the best therapeutic benefits for patients. [ABSTRACT FROM AUTHOR]

Background: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. Objectives: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. Methods: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. Outcome: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. Conclusions and Outlook: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the quality of laparoscopic myomectomy videos on YouTube and WebSurg. Material and Methods: We searched using the keyword "laparoscopic myomectomy" on WebSurg and selected surgical interventions in the gynecology section. Eleven videos on WebSurg were enrolled. We selected the 22 most-relevant videos on YouTube to create a comparison group, with a ratio of 1:2. Sound in videos, number of subscribers, views, likes, and comments, number of days since videos were uploaded and durations of videos were recorded. View/day, like/view, like/subscriber, and view/subscriber ratios were calculated. The videos were evaluated with usefulness score (US), global quality scoring (GQS), modified discern score (mDS) and laparoscopic surgery video educational guidelines (LAP-VEGaS). Results: The view/day ratio was lower in WebSurg compared to YouTube [1.3 (1.9) vs. 7.5 (30.6), respectively; p=0.039]. No difference was found between WebSurg and YouTube in terms of US, GQS and mDS. On LAP-VEGaS assessment, WebSurg was found to be superior to YouTube in terms of intraoperative findings [2 (1-2) vs. 1 (0-2), p=0.001], additional materials [1 (0-2) vs. 1 (0-1), p=0.041], audio/written commentary [2 (2-2) vs. 2 (0-2), p=0.037], image quality [2 (2-2) vs. 2 (0-2), p=0.023], questions and total score [12 (11-13) vs. 10.5 (4-13), p=0.006]. The proportion of high-quality video was higher in WebSurg compared to YouTube, when the cut-off value of total score of 11 or 12 was used as 10 (100%) vs. 10 (50%), p=0.011 and 9 (90%) vs. 5 (25%), p=0.001, respectively. Conclusion: WebSurg was better compared to YouTube in terms of quality of laparoscopic myomectomy videos. [ABSTRACT FROM AUTHOR]

Copyright of Health & Society is the property of Instituto de Ensino e Pesquisa Periodicojs and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)