Disseminated peritoneal leiomyoma: a diagnostic dilemma.

Disseminated peritoneal leiomyomatosis (DPL) is a rare and benign clinical entity. It is also known as leiomyomatosis peritonealis disseminata (LPD). Here, we report and discuss a case of a primiparous woman in her early 40s who presented with heavy, prolonged, painful menses and heaviness in her lower abdomen. She underwent a laparoscopic myomectomy for a fibroid uterus, 12 months ago for similar complaints. On workup, she was diagnosed with DPL. We performed a total abdominal hysterectomy with bilateral salpingectomy, low anterior resection with stapled colorectal anastomosis and excision of peritoneal tumour deposits in consortium with the gastrosurgery team. Her postoperative period was uneventful, and the patient was discharged on postop day 6. Her histopathology report was consistent with leiomyoma; the follow-up period was uneventful.

Giant complete hydatidiform mole: a case report and review of the literature.

BACKGROUND: This case describes the youngest patient documented in the literature who presented with a giant hydatidiform mole, effectively addressed through conservative treatment. CASE PRESENTATION: Our department received a 20-year-old Caucasian patient who was admitted due to significant metrorrhagia in an undisclosed pregnancy. During examination, we identified a massive, highly vascularized hydatidiform mole measuring 22 cm (cm). We performed a surgical dilatation and curettage. The anatomopathological findings confirmed the presence of a complete hydatidiform mole (CHM). Following the established guidelines, we conducted weekly monitoring of human chorionic gonadotropin (hCG). Unfortunately, the patient discontinued the follow-up and became pregnant again before achieving hCG negativation. CONCLUSION: This case suggests that conservative treatment is a viable option regardless of the size of gestational trophoblastic disease (GTD), especially when the preservation of fertility is a crucial consideration, as effectively demonstrated in our case.

Heterotopic pregnancy: a case report of intrauterine hydatidiform mole with tubal pregnancy.

We herein report a rare case of simultaneous intrauterine molar pregnancy and tubal pregnancy. A woman of childbearing age who had never been pregnant underwent an ultrasound examination 70 days after the onset of menopause. She had a history of ovulation induction. The ultrasound findings suggested a partial hydatidiform mole. She was then pathologically confirmed to have a complete hydatidiform mole after uterine suction dilation and curettage. On postoperative day 4, an ultrasound examination before discharge showed an inhomogeneous mass in the left adnexal region with mild lower abdominal pain. On postoperative day 17, the blood human chorionic gonadotropin level did not drop as expected, and a follow-up examination still indicated a mass in the left adnexal region. We were unable to rule out an ectopic hydatidiform mole. Hysteroscopy with laparoscopic exploration of the left adnexal mass and salpingotomy suggested a diagnosis of intrauterine hydatidiform mole combined with left tubal pregnancy.

A Case Report of Uterine Torsion in a Postmenopausal Female with a Large Leiomyoma.

This case report discusses a diagnosis of uterine torsion in an 84-year-old woman who presented with five days of right lower quadrant abdominal pain, nausea, vomiting, constipation, and poor intake. Computed tomography (CT) imaging demonstrated a whorled configuration at the junction of the cervix and lower uterine segment, with the left gonadal vein crossing midline, and two previously known right leiomyomas now appearing on the left. These findings were consistent with the diagnosis of uterine torsion. She then underwent an urgent exploratory laparotomy, and the uterus was found to be dextroverted 270 degrees, with dark mottled purple tissue and engorged vessels. A supracervical hysterectomy and bilateral salpingo-oopherectomy were performed. Final pathology demonstrated extensive necrosis. This case reviews the classic presentation and imaging findings for the rare diagnosis of uterine torsion and options for management of both non-gravid and gravid patients.

Retroperitoneal dermoid cyst complicated with uterine adenomyoma: a case report and literature review.

Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.

Invasive and metastatic hydatidiform moles in Slovakia in 1993‒2022.

OBJECTIVE: A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes. BACKROUND: Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy. METHODS: Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission. RESULTS: The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters. CONCLUSION: First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).

2­D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells.

2',3',4'­trihydroxyflavone (2­D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma (Ut­LMS) are unknown. The anticancer activity of 2­D08 was explored in an in vitro model using SK­LMS­1 and SK­UT­1B cells (human Ut­LMS cells). Treatment with 2­D08 inhibited cell viability in a dose­ and time­dependent manner and significantly inhibited the colony­forming ability of Ut­LMS cells. In SK­UT­1B cells treated with 2­D08, flow cytometric analysis revealed a slight increase in apoptotic rates, while cell cycle progression remained unaffected. Western blotting revealed elevated levels of RIP1, indicating induction of necrosis, but LC3B levels remained unchanged, suggesting no effect on autophagy. A lactate dehydrogenase (LDH) assay confirmed increased LDH release, further supporting the induction of apoptosis and necrosis by 2­D08 in SK­UT­1B cells. 2­D08­induced production of reactive oxygen species and apoptosis progression were observed in SK­LMS­1 cells. Using Ki67 staining and bromodeoxyuridine assays, it was found that 2­D08 suppressed proliferation in SK­LMS­1 cells, while treatment for 48 h led to cell­cycle arrest. 2­D08 upregulated p21 protein expression in SK­LMS­1 cells and promoted apoptosis through caspase­3. Evaluation of α­SM­actin, calponin 1 and TAGLN expression indicated that 2­D08 did not directly initiate smooth muscle phenotypic switching in SK­LMS­1 cells. Transcriptome analysis on 2­D08­treated SK­LMS­1 cells identified significant differences in gene expression and suggested that 2­D08 modulates cell­cycle­ and apoptosis­related pathways. The analysis identified several differentially expressed genes and significant enrichment for biological processes related to DNA replication and molecular functions associated with the apoptotic process. It was concluded that 2­D08 exerts antitumor effects in Ut­LMS cells by modulating multiple signaling pathways and that 2­D08 may be a promising candidate for the treatment of human Ut­LMS. The present study expanded and developed knowledge regarding Ut­LMS management and indicated that 2­D08 represents a notable finding in the exploration of fresh treatment options for such cancerous tumors.

Comparative Analysis of Shapley Values Enhances Transcriptomics Insights across Some Common Uterine Pathologies.

Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

Pulmonary metastatic gestational choriocarcinoma following an uncomplicated term pregnancy: a case report.

BACKGROUND: Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies). CASE PRESENTATION: We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of ß-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process. CONCLUSION: The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy.

Comparison of uterine myometrial thickness at the site of myomectomy scar after surgery using laparoscopic and laparotomy methods.

Fibroids are the most common benign tumours of the uterus, often requiring surgery when symptomatic. This study aims to investigate the impact of surgery using two methods, laparoscopy and laparotomy, on the thickness and vascularity of the uterine myometrium at the site of myomectomy scar (comparing sonographic features at the surgical scar site, including thickness, vascularity, and the extent of fibrotic tissue, in both open and laparoscopic surgical approaches). In this clinical trial, 100 women with type 2-5 fibroids and clinical symptoms, seeking surgery et al. Zahra Hospital, were enrolled in two groups: laparoscopy and laparotomy. Inclusion criteria were a maximum fibroid size of 8 cm and, in the case of multiple fibroids, a maximum of three, with the largest being 8 cm. 6 months post-surgery, sonographic assessments of the myomectomy scar site were compared between both groups. Participants showed no significant differences in demographic and obstetric factors. The most common clinical symptom (87%) in both groups was abnormal uterine bleeding (AUB). The mean hospital stay duration was statistically significantly lower in the laparoscopy group at 1.64 (SD 0.56) compared to 1.89 (SD 0.58) in the laparotomy group (p = 0.028). Additionally, the decrease in haemoglobin levels was 0.89 (SD 0.92) and 1.87 (SD 2.24) units, respectively, which showed a statistically significant difference (p = 0.003). The duration of surgery was significantly shorter in the laparotomy group (p = 0.001). Abdominal pressure was not observed in the laparoscopy group, while 12% of the laparotomy group reported complaints (p = 0.013). Based on the results obtained in this study, it can be concluded that there was no difference between these two methods in terms of improving uterine thickness and associated complications. However, the decrease in haemoglobin levels and the length of hospital stay were lower in patients undergoing laparoscopy.

Single-nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis.

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three-allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single-nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three-allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

Solving the mysteries surrounding uterine fibroids: are we almost there?

A better understanding of uterine fibroid-related pathogenesis and symptoms like uterine bleeding and infertility is mandatory.

Killer Function of Circulating Neutrophils in Relation to Cytokines in Uterine Myoma and Endometrial Cancer.

The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).

Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and "suicide gene therapy" to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options.

Choriocarcinoma in neonates and infants: A severe but curable disease.

Choriocarcinoma in neonates and infants (N-CC) is an extremely rare, but aggressive cancer, frequently observed with concomitant maternal disease. A retrospective, bi-national study of patients treated in France and Poland for infantile choriocarcinoma analysed eight cases of N-CC, median age of 6 weeks. All tumours were diffuse. Six patients received a platinum-based regimen, and five had delayed surgery on residual distant tumour sites. At the end of follow-up, four patients were in complete remission and four had died of the disease. In all but two cases, mothers had simultaneous metastatic choriocarcinoma. Even if the outcome remains poor, patients could be cured with multimodal therapy.

Targeting the long non-coding RNA MIAT for the treatment of fibroids in an animal model.

Our previous studies indicated that there is overexpression of MIAT in fibroids and MIAT is a sponge for the miR-29 family in these tumors. The objective of the present study was to determine if the knockdown of MIAT in fibroid xenografts will increase miR-29 levels and reduce the expression of genes targeted by this miRNA such as collagen and cell cycle regulatory proteins in a mouse model for fibroids. Ovariectomized CB-17 SCID/Beige mice bearing estrogen/progesterone pellets were implanted subcutaneously in the flank with equal weight of fibroid explants which had been transduced by lentivirus for either control (empty vector) or MIAT knockdown for four weeks (n=7). Knockdown of MIAT in fibroid xenografts resulted in a 30% reduction of tumor weight and a marked increase in miR-29a, -b, and -c levels in the xenografts. There was reduced cell proliferation and expression of cell cycle regulatory genes CCND1, CDK2, and E2F1 and no significant changes in apoptosis. The xenografts with MIAT knockdown expressed lower mRNA and protein levels of FN1, COL3A1, and TGF-ß3, and total collagen protein. Targeting MIAT, which sponges the pro-fibrotic miR-29 family, is an effective therapy for fibroids by reducing cell proliferation and thereby, tumor growth and accumulation of ECM, which is a hallmark of these benign gynecologic tumors.

Long-term outcome and fertility results of intraplacental choriocarcinoma: a retrospective study of 14 patients and literature review.

BACKGROUNDS: Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. RESULTS: Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of "fear and worry about choriocarcinoma recurrence". We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. CONCLUSIONS: IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. CLINICAL TRIAL REGISTRATION: N/A.

Potential Markers to Differentiate Uterine Leiomyosarcomas from Leiomyomas.

Uterine leiomyomas (ULM) are the most common benign tumors of the female genitalia, while uterine leiomyosarcomas (ULMS) are rare. The sarcoma is diffuse growth, prone to hematogenous metastasis, and has a poor prognosis. Due to their similar clinical symptoms and morphological features, it is sometimes difficult to distinguish them, and the final diagnosis depends on histological diagnosis. Misdiagnosis of ULM as ULMS will lead to more invasive and extensive surgery when it is not needed, while misdiagnosis of ULMS as ULM may lead to delayed treatment and poor prognosis. This review searched and studied the published articles on ULM and ULMS, and summarized the potential markers for the differential diagnosis of ULMS. These markers will facilitate differential diagnosis and personalized treatment, providing timely diagnosis and potentially better prognosis for patients.