High-dose ascorbate exerts anti-tumor activities and improves inhibitory effect of carboplatin through the pro-oxidant function pathway in uterine serous carcinoma cell lines.

OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.

Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System.

OBJECTIVE: To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. METHODS: We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. RESULTS: Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. CONCLUSION: Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.

Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021.

BACKGROUND: In Japan, comprehensive cancer statistics data have been collected through national cancer registries, but these data are rarely summarized and reported in research articles. METHODS: Here, we compiled the national registry data on malignant tumors originating from gynecologic organs (ovary, corpus uteri, cervix uteri) in Japan. RESULTS: The number of new patients in 2019 was 13,380, 17,880, and 10,879, respectively, and the number of deaths in 2021 was 5081, 2741, and 2894, respectively. Compared with 40 years ago, the incidence of ovarian cancer has tripled, the incidence of uterine corpus cancer (mainly endometrial cancer) has increased eightfold, the mortality rate of uterine corpus cancer has tripled, and the incidence of cervical intraepithelial cancer has increased ninefold in data standardized by the world population. Compared with the United States, the incidence rate of ovarian cancer has overtaken and the mortality rate of uterine corpus cancer is the same, while both the incidence and mortality rates of cervical cancer are higher in Japan. CONCLUSION: The incidence of gynecologic cancer is increasing significantly in Japan.

Considerations on implementation of the newest treatment for symptomatic uterine fibroids: Oral GnRH antagonists.

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.

Atypical Placental Site Nodules within the Diverticulum of the Uterine Incision, a Rare Gestational Trophoblastic Disease Misdiagnosed as Intrauterine Residue: A Case Report.

Atypical placental site nodule (APSN) is a rare benign gestational trophoblastic disease (GTD). It is a tumor-like transformation that has a certain probability of developing into a placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT). Because of its atypical clinical presentation, it is difficult to diagnose and susceptible to misdiagnosis highly, thus delaying the patient's condition. We report a scarce case of atypical nodules at the placental site of the uterine incision diverticulum in a 35-year-old female, who was irregular vaginal bleeding after a cesarean Sect. 2 years. She was diagnosed by several local hospitals with intrauterine residue and was given a variety of Traditional Chinese Medicine (TCM) orally, but the symptoms of irregular vaginal bleeding have not been alleviated. After being transferred to several hospitals, she went to Hubei Maternal and Child Health Hospital for treatment. Under the condition of excluding the second pregnancy, she underwent hysteroscopic resection of lesions and laparoscopic repair of uterine incision diverticulum. The pathological diagnosis after the operation suggested that the focus at the uterine incision was an atypical placental nodule that invaded the myometrium of the uterus. The operation completely removed the focus, and then the patient was followed up every 3 months in the first postoperative year, then every 6 months up to 3 years, and then annually thereafter up to 5 years, and then maybe every 2 years thereafter. The patient's condition was quickly controlled, and the prognosis was good.

Hysteroscopic diode laser myolysis: from a case series to literature review of incisionless myolysis techniques for managing heavy menstrual bleeding in premenopausal women.

PURPOSE: This case series examined the safety and effectiveness of hysteroscopic myolysis using laser-induced interstitial thermo-therapy (LITT) for treating heavy menstrual bleeding (HMB) in premenopausal women with FIGO type 1 or 2 uterine fibroids, not planning for future fertility. Additionally, a comprehensive review of innovative, minimally invasive, incisionless myolysis techniques was conducted. METHODS: Women with HMB, sonographically diagnosed with a single FIGO type 1 or 2 fibroid, underwent hysteroscopic myolysis using the Leonardo® diode laser. Effectiveness was assessed via transvaginal ultrasound measurement of myoma size, volume and vascularization pre and post-procedure. Moreover, we also evaluated any improvements in symptoms using the Pictorial Blood Loss Assessment Chart (PBAC score) scores. RESULTS: The procedure resulted in significant HMB reductions and noticeable fibroid size, volume, and vascularization decrease in all three patients, with no reported complications. The literature review revealed both advantages and limitations of the minimally invasive, incisionless myolysis techniques. CONCLUSIONS: Hysteroscopic laser myolysis is a safe and effective therapeutic intervention for patients experiencing HMB, diagnosed with FIGO type 1 or 2 fibroids, and not planning for future fertility. The procedure resulted in significant reductions in menstrual blood loss and fibroid size. Despite the promising results, it is essential to note the limitations of this report, including its case series design, a small number of patients, and a short follow-up period. Further research is necessary to confirm these results.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Association of metabolic syndrome conditions with risk of second primary uterine cancer in breast cancer survivors.

PURPOSE: Uterine cancer risk is high in breast cancer survivors. Although breast cancer and uterine cancer share some common epidemiological risk factors, association of metabolic syndrome with incident uterine cancer in breast cancer survivors is under-studied. We evaluated the association of metabolic syndrome conditions with second primary uterine cancer in breast cancer survivors. METHODS: In this retrospective cohort study, 37,303 breast cancer patients diagnosed between 2008 and 2020 at Kaiser Permanente Southern California, an integrated healthcare system, were included. Data on cancer-related variables, sociodemographic, and clinical variables were extracted from KPSC's Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry and electronic health records, as appropriate. Patients were followed from breast cancer diagnosis until 12/31/2021 for incident uterine cancer. Proportional hazards regression was used to report association [HR (95% CI)] between metabolic conditions and uterine cancer. RESULTS: More than half (53.1%) of the breast cancer survivors had 1-2 metabolic conditions; 19.4% had 3 + , while 27. 5% had no metabolic conditions. Median time to follow-up was 5.33 years and 185 (0.5%) patients developed second primary uterine cancer. Obesity was associated with an elevated uterine cancer risk in the adjusted model [HR (95% CI) 1.64 (1.20-2.25)]. Having 1-2 metabolic conditions (versus none) was not associated with increased uterine cancer risk [adjusted HR (95% CI) 1.24 (0.85-1.82)]; however, there was an increased uterine cancer risk with 3 + metabolic conditions [adjusted HR (95% CI) 1.82 (1.16-2.87)]. CONCLUSION: Although not statistically significant, we found a trend demonstrating greater uterine cancer risk by increasing numbers of metabolic syndrome conditions in breast cancer survivors.

Surgical management of uterine fibroids.

PURPOSE OF REVIEW: Fibroids are benign pelvic masses and constitute the most common gynaecological condition. They create a significant health and social burden to many women because of heavy menstrual bleeding and fibroid pressure symptoms. Many women will be faced with the dilemma of surgical management to improve their symptoms at some point of their reproductive age. The aim of this article is to identify current surgical management of fibroids describing the technical steps, advantages, disadvantages and risks of each method. RECENT FINDINGS: The surgical management of fibroids remains challenging, as the overall prevalence, the clinical experience and the patient awareness is increasing because of an upgrade in our sonographic and magnetic resonance diagnostic tools. Unfortunately not every patient is able to benefit from tailor-made surgery that holistically evaluates individual needs including fertility aspirations. SUMMARY: This article provides the most current synopsis of every available surgical modality for fibroid management. Large prospective multicentre cohort studies are needed to definitely determine the most suitable operation for any individual suffering with fibroids; and perhaps artificial intelligence may offer a valuable tool in the future data analysis.

Ameliorative effects of a Chinese herbal formula, fufang meidengmu on uterine leiomyoma in a mice model.

Fufang Meidengmu (FFMDM) is an ethnic herbal medicine form Yunnan province of China, which is often used for the treatment of uterine leiomyoma (UL). Combined Gancao (Glycyrrhiza uralensis Fisch.) and Haizao (Sargassum pallidum (Turn.) C.Ag) in FFMDM represent an herbal pair in the so-called "eighteen antagonistic medicaments" according to traditional Chinese medicine. In this study, we explored the prevention and treatment effects of FFMDM component compatibility on UL in mice. Female Kunming mice were injected for different periods of time with different concentrations of estradiol benzoate (EB) to investigate a feasible method to establish a mice model of UL. Treatment with 0.3mg/kg EB for 15 days was found to be the optimal condition for UL mice models. We then investigate the role of Gancao and Haizao in FFMDM, and explored the underlying mechanism of action of UL mice. Our findings suggested that Gancao and Haizao exerted the favorable effects. In addition, FFMDM is effective in the treatment of UL, and its mechanism was associated with the estrogen (ER) and progesterone receptors (PR).

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy.

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

Contemporary approaches in the management of uterine leiomyomas.

BACKGROUND: Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention. OBJECTIVE: Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas. SEARCH STRATEGY: PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA). RESULTS: Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas. CONCLUSION: Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.

Mapa de evidências efetividade clínica das Medicinas Tradicionais, Complementares e Integrativas para Câncer do Útero: informe executivo / Map of evidence clinical effectiveness of Traditional, Complementary and Integrative Medicines for Uterine Cancer: executive report

O mapa apresenta uma visão geral das evidências sobre os efeitos clínicos das terapias complementares e integrativas para o câncer do útero e do colo do útero. A partir da caracterização de centenas de estudos na série de mapas de evidências das Medicinas Tradicionais, Complementares e Integrativas (MTCI/PICS), foram selecionados e incluídos 26 estudos de revisão (18 revisões sistemáticas, 7 revisões sistemáticas e metanálises, e 1 metanálise). As revisões avaliaram o efeito de 28 tipos de intervenções distribuídos em 3 grupos ­ Fitoterapia e Plantas Medicinais; Terapias não-Farmacológicas; Suplementos / Produtos Naturais ­ e associadas a 33 desfechos de saúde distribuídos em 5 grupos: Curso da doença; Sintomas relacionados ao Câncer; Indicadores Metabólicos e Fisiológicos; Bem-Estar, Vitalidade e Qualidade de Vida; Saúde Mental.

Complementary and Alternative Medicine Use Among Women with Symptomatic Uterine Fibroids.

Objective: The aim of this study is to examine complementary and alternative medicine (CAM) use among women with symptomatic uterine fibroids in the United States. Materials and Methods: In this cross-sectional analysis of baseline data from a multicenter, prospective cohort study of premenopausal women undergoing surgery for symptomatic fibroids and who enrolled in the Uterine Leiomyoma Treatment with Radiofrequency Ablation study from 2017 to 2019, we contrast women indicating use of at least one CAM modality specifically for fibroid symptoms against women using CAM for other reasons and CAM nonusers. Multivariable logistic regression models were performed to identify participant characteristics independently associated with CAM use for fibroids. Results: Among 204 women, 55% were Black/African American and the mean age was 42 (standard deviation 6.6) years. CAM use was common (67%), with 42% (95% confidence interval [CI]: 35%-49%) reporting use of CAM specifically to treat fibroid symptoms. Most commonly, CAM treatments used for fibroids were diet (62%) and herbs (52%), while CAM treatments for other reasons were exercise (80%) and massage (43%). On average, each participant who reported CAM use utilized three different types of CAM modalities. In a multivariable model, participants were more likely to use CAM for fibroids if they had pelvic pressure (odds ratio [OR] 2.50, 95% CI: 1.07-5.87, p = 0.04), a body-mass index lower than average (OR 0.76, 95% CI: 0.60-0.97, p = 0.03), and a lower health-related quality of life score (OR 0.61, 95% CI: 0.46-0.81, p = 0.001). Conclusions: In this diverse sample of women with symptomatic fibroids, CAM use was highly prevalent. Our findings highlight the need for providers to query patients about CAM use and understand the role of CAM in fibroid management. ClinicalTrials.gov Identifier: NCT02100904.

Diagnosis and management of uterine fibroids: current trends and future strategies.

Uterine fibroids (UFs), leiomyomas or myomas, are a type of malignancy that affects the smooth muscle of the uterus, and it is most commonly detected in women of reproductive age. Uterine fibroids are benign monoclonal growths that emerge from uterine smooth muscle cells (myometrium) as well as fibroblasts. Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation. It is also associated with reproductive issues like impaired fertility, conceiving complications, and adverse obstetric outcomes. It is the leading cause of gynaecological hospitalisation in the American subcontinent and a common reason for the hysterectomy. Twenty-five percent of the reproductive women experience the symptoms of uterine fibroids, and among them, around 25% require hospitalization due to the severity of the disease. The frequency of the disease remains underestimated as many women stay asymptomatic and symptoms appear gradually; therefore, the condition remains undiagnosed. The exact frequency of uterine fibroids varies depending on the diagnosis, and the population investigated; nonetheless, the incidence of uterine fibroids in reproductive women ranges from 5.4 percent to 77 percent. The uterine fibroid treatment included painkillers, supplementation with iron, vitamin D3, birth control, hormone therapy, gonadotropin-releasing hormone (GnRH) agonists, drugs modulating the estrogen receptors, and surgical removal of the fibroids. However, more research needed at the level of gene to get a keen insight and treat the disease efficiently.

HER2 IHC Expression and Gene Amplification in p53-aberrant High-grade Endometrial Endometrioid Carcinoma Suggests That This Population May Benefit From HER2 Testing and Targeted Therapy.

Among gynecologic cancers, uterine serous carcinoma (USC) has been shown to be human epidermal growth factor receptor 2 (HER2) amplified and trastuzumab has been included in the recent National Comprehensive Cancer Network (NCCN) guidelines for treatment of advanced stage or recurrent USC with HER2 overexpression/amplification. There is limited literature suggesting that a subset of high-grade endometrioid carcinomas with aberrant p53 expression may also be HER2 amplified and these patients could benefit from the addition of targeted therapy. We identified 59 p53-aberrant (mismatch repair proficient) FIGO 3 endometrioid carcinomas of the uterus. HER2 immunohistochemistry was performed in all 59 tumors and HER2 fluorescence in situ hybridization (FISH) was performed in 52 of the 59 cases. Four of the 59 cases were HER2 3+ by immunohistochemistry (6.7%), using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2007, 2013, and 2018 criteria. HER2 FISH was performed in 3 of the 4 cases and was amplified in all 3. Nine, 8, and 7 tumors showed 2+ HER2 staining when applying 2018, 2013, and 2007 criteria, respectively, FISH was performed in 7 tumors and none were amplified. An additional 4 cases did not perfectly meet the 2018 ASCO/CAP criteria but were assigned a score of 2+, none were amplified by HER2 FISH. The remaining 42 cases showed 1+ or no staining for HER2, FISH was successfully performed in 38 tumors and none showed amplification. Approximately half of the tumors fulfilled criteria for HER2-low or HER2-very low (10 HER2-low and 20 HER2-very low). Our data shows that a subset of p53-aberrant high-grade endometrial endometrioid carcinoma express HER2 and these patients may benefit from the addition of targeted therapy. The role of targeted therapy in HER2-low gynecologic carcinoma is currently unexplored.

Differential diagnosis of uterine adenosarcoma: identification of JAZF1-BCORL1 rearrangement by comprehensive cancer genomic profiling.

BACKGROUND: Uterine adenosarcoma is a rare malignant tumor that accounts for 8% of all uterine sarcomas, and less than 0.2% of all uterine malignancies. However, it is frequently misdiagnosed in clinical examinations, including pathological diagnosis, and imaging studies owing to its rare and non-specific nature, which is further compounded by the lack of specific diagnostic markers. CASE PRESENTATION: We report a case of uterine adenosarcoma for which a comprehensive genomic profiling (CGP) test provided a chance to reach the proper diagnosis. The patient, a woman in her 60s with a history of uterine leiomyoma was diagnosed with an intra-abdominal mass post presentation with abdominal distention and loss of appetite. She was suspected to have gastrointestinal stromal tumor (GIST); the laparotomically excised mass was found to comprise uniform spindle-shaped cells that grew in bundles with a herringbone architecture, and occasional myxomatous stroma. Immunostaining revealed no specific findings, and the tumor was diagnosed as a spindle cell tumor/suspicious adult fibrosarcoma. The tumor relapsed during postoperative follow-up, and showed size reduction with chemotherapy, prior to regrowth. CGP was performed to identify a possible treatment, which resulted in detection of a JAZF1-BCORL1 rearrangement. Since the rearrangement has been reported in uterine sarcomas, we reevaluated specimens of the preceding uterine leiomyoma, which revealed the presence of adenosarcoma components in the corpus uteri. Furthermore, both the uterine adenosarcoma and intra-abdominal mass were partially positive for CD10 and BCOR staining. CONCLUSION: These results led to the conclusive identification of the abdominal tumor as a metastasis of the uterine adenosarcoma. The JAZF1-BCORL1 rearrangement is predominantly associated with uterine stromal sarcomas; thus far, ours is the second report of the same in an adenosarcoma. Adenosarcomas are rare and difficult to diagnose, especially in atypical cases with scarce glandular epithelial components. Identification of rearrangements involving BCOR or BCORL1, will encourage BCOR staining analysis, thereby potentially resulting in better diagnostic outcomes. Given that platinum-based chemotherapy was proposed as the treatment choice for this patient post diagnosis with adenosarcoma, CGP also indirectly contributed to the designing of the best-suited treatment protocol.

Soy-Based Infant Formula Feeding and Uterine Fibroid Development in a Prospective Ultrasound Study of Black/African-American Women.

BACKGROUND: Uterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding. OBJECTIVE: The goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood. METHODS: We evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids ≥0.5cm in diameter. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between soy formula feeding and incident fibroids adjusted for early-life and adult factors. Fibroid growth was calculated as change in log-volume for fibroids matched at successive visits. RESULTS: Of 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (HR=1.08; 95% CI: 0.75, 1.54). However, participants fed soy formula within 2 months of birth and for >6 months (n=53) had an elevated risk of fibroid incidence in comparison with those never fed soy formula (HR=1.56; 95% CI: 0.92, 2.65). Fibroid growth rates did not differ. DISCUSSION: Adding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.

A Systematic Review of Minimally Invasive Approaches to Uterine Fibroid Treatment for Improving Quality of Life and Fibroid-Associated Symptoms.

Improvement in symptom severity and quality of life (QoL) are critical concerns for women with fibroids as they evaluate treatment options. This systematic review analyzed available evidence regarding minimally invasive approaches to fibroid treatment and compared validated QoL and fibroid-associated symptom scores before and after treatment. A comprehensive search was conducted using PubMed, Embase, Cochrane Library, and Scopus from January 1990 to July 2020. English-language publications were included if they evaluated associations between minimally invasive approaches to fibroid treatment and QoL or fibroid-associated symptoms, and they used validated questionnaires before and after treatment. QoL or fibroid-associated symptom scores were compared and summarized for each minimally invasive approach. Thirty-seven studies were ultimately included in this review: 26 evaluating individual approaches and 11 which were comparative studies of minimally invasive approaches and surgical interventions. Radiofrequency ablation (RFA) and ultrasound-guided sclerotherapy (USGS) significantly improved overall QoL. Uterine artery embolization (UAE) and ultrasound-guided high-intensity frequency ultrasound (US-HIFU) improved overall QoL to a similar extent as surgical interventions. Twenty-eight studies assessed fibroid-associated symptoms with the Uterine Fibroid Symptoms Quality of Life Questionnaire (UFS-QoL). UAE, magnetic resonance imaging-guided high-intensity frequency ultrasound (MR-HIFU), US-HIFU, RFA, and percutaneous microwave ablation (PMWA) significantly decreased Symptom Severity Score by a range of 21 to 39 points (out of 100) at 6 months. Minimally invasive approaches to treat fibroids were effective alternatives to surgical interventions for improving quality of life, fibroid-associated symptoms, and pain. Outcomes among minimally invasive approaches were similar, presenting patients with numerous options for fibroid treatment.

Targeted Therapies in the Treatment of Uterine Serous Carcinoma.

OPINION STATEMENT: Despite the dismal prognosis of uterine serous carcinoma (USC), recent advances in molecular classification and targeted treatments have demonstrated improvements in survival outcomes for patients both in the upfront and recurrent treatment settings. After appropriate surgical staging and surgical cytoreduction as indicated, correct pathologic and molecular classification of USC is important to provide the most appropriate systemic adjuvant treatment. HER2-targeted agents are one of the most important advances in the treatment of USC in decades. Thus, for HER2-positive tumors, the addition of trastuzumab to conventional chemotherapy is indicated in those with advanced stage and/or recurrent disease. Treatment with pembrolizumab and lenvatinib suggests a 50% response rate in women with recurrent disease which serves as a promising targeted treatment strategy. Overall, emerging targeted therapeutic options with antibody-drug conjugates (i.e. targeting HER2, folic acid receptor alpha, or Trop-2), combinations of immunotherapies and tyrosine kinase inhibitors, PARP inhibitors, WEE1 inhibitors, and AKT inhibitors shed further promise in advancements of effective disease-modifying treatments for this unmet medical need for patients with USC. Several trials evaluating these targeted agents are ongoing, and those results are eagerly awaited. As such, enrollment of patients in clinical trials is highly recommended as it will provide patients with a higher level of personalized cancer care.