In Vivo Effects of Bay 11-7082 on Fibroid Growth and Gene Expression: A Preclinical Study.

Current medical therapies for fibroids have major limitations due to their hypoestrogenic side effects. Based on our previous work showing the activation of NF-kB in fibroids, we hypothesized that inhibiting NF-kB in vivo would result in the shrinkage of tumors and reduced inflammation. Fibroid xenografts were implanted in SCID mice and treated daily with Bay 11-7082 (Bay) or vehicle for two months. Bay treatment led to a 50% reduction in tumor weight. RNAseq revealed decreased expression of genes related to cell proliferation, inflammation, extracellular matrix (ECM) composition, and growth factor expression. Validation through qRT-PCR, Western blotting, ELISA, and immunohistochemistry (IHC) confirmed these findings. Bay treatment reduced mRNA expression of cell cycle regulators (CCND1, E2F1, and CKS2), inflammatory markers (SPARC, TDO2, MYD88, TLR3, TLR6, IL6, TNFα, TNFRSF11A, and IL1ß), ECM remodelers (COL3A1, FN1, LOX, and TGFß3), growth factors (PRL, PDGFA, and VEGFC), progesterone receptor, and miR-29c and miR-200c. Collagen levels were reduced in Bay-treated xenografts. Western blotting and IHC showed decreased protein abundance in certain ECM components and inflammatory markers, but not cleaved caspase three. Ki67, CCND1, and E2F1 expression decreased with Bay treatment. This preclinical study suggests NF-kB inhibition as an effective fibroid treatment, suppressing genes involved in proliferation, inflammation, and ECM remodeling.

Analysis of Expression of the ANG1, CaSR and FAK Proteins in Uterine Fibroids.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

Leiomyoma of submandibular gland.

Leiomyoma is a benign tumour of smooth muscle origin. Leiomyoma arising in major salivary gland is under-reported. We report a case of a woman in her 40s with a submandibular gland tumour which represented a diagnostic challenge during preoperative assessment. The core needle biopsy of submandibular gland tumour revealed a spindle cell tumour suggestive of an undifferentiated tumour. As a malignancy could not be excluded, the submandibular gland tumour was removed en bloc with surrounding lymph nodes in level Ib of the neck. Leiomyoma may be included in the differential diagnosis of spindle cell salivary gland tumours, particularly when there are no signs of infiltration and preoperative investigations are inconclusive.

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.

Intramural Leiomyomas and Fertility: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate fertility outcomes based on size and number of intramural leiomyomas and outcomes after removal. DATA SOURCES: Online searches: MEDLINE, ClinicalTrials.gov , PubMed, Cochrane Library, and PROSPERO Library from 1994 to 2023. METHODS OF STUDY SELECTION: A total of 5,143 studies were identified, with inclusion of 13 study groups. TABULATION, INTEGRATION AND RESULTS: Outcomes for size and number of leiomyomas were reported with clinical pregnancy rates and ongoing pregnancy or live-birth rates. In data sets with maximum leiomyoma diameters of less than 6 cm for study inclusion, women with leiomyomas smaller than 3 cm had lower clinical pregnancy rates than women without leiomyomas, with an odds ratio (OR) of 0.53 (95% CI, 0.38-0.76) and, for ongoing pregnancy or live-birth rates, an OR of 0.59 (95% CI, 0.41-0.86). The ORs for clinical pregnancy rates in women with intermediately-sized leiomyomas (those between 3 cm and 6 cm) were lower than in women without leiomyomas, with an OR at 0.43 (95% CI, 0.29-0.63) and, for ongoing pregnancy or live-birth rates, an OR at 0.38 (95% CI, 0.24-0.59). In data sets without exclusion for women with larger-sized leiomyomas, clinical pregnancy rates were lower for those with leiomyomas smaller than 5 cm compared with those without leiomyomas, with an OR of 0.75 (95% CI, 0.58-0.96). Women with leiomyomas larger than 5 cm showed no differences in clinical pregnancy rate compared with women without leiomyomas, with an OR of 0.71 (95% CI, 0.32-1.58). Although women with a single leiomyoma in any location had no differences in outcomes, those with more than one leiomyoma had lower clinical pregnancy rates and ongoing pregnancy or live-birth rates, with an OR of 0.62 (95% CI, 0.44-0.86) and 0.57 (95% CI, 0.36-0.88), respectively. The clinical pregnancy rate for women undergoing myomectomy for intramural leiomyomas was no different than those with intramural leiomyomas in situ, with an OR of 1.10 (95% CI, 0.77-1.59). CONCLUSION: Even small intramural leiomyomas are associated with lower fertility; removal does not confer benefit. Women with more than one leiomyoma in any location have reduced fertility.

Preterm birth and uterine fibroid necrosis: The clinical presentation illustrated in a case series.

OBJECTIVE: Uterine fibroids increase the risk of preterm birth. The current study highlights uterine fibroid necrosis as a possible cause of (extreme) preterm birth. STUDY DESIGN: Retrospective cohort study in one Dutch academic hospital. Cases were selected from the 526 participants of the MyoFert study (Netherlands Trial Register, NL7990), which included patients who presented between 2004 and 2018 and were between the age of 18 and 45 years at the time of diagnosis of uterine fibroids. Of these participants, 414 women became pregnant. A retrospective chart review of the first pregnancies was performed. The main outcomes were (imminent) preterm birth and signs of fibroid necrosis on ultrasound. In women with signs of fibroid necrosis, the following data were collected systematically: fibroid characteristics, clinical presentation, pregnancy outcome, and postpartum period. RESULTS: In total, 66 women had a preterm birth (16 %, 66/414), of which 25 pregnancies ended between 16 and <24 weeks (38 %, 25/66) and 41 pregnancies ended between 24 and <37 weeks of gestation (62 %, 41/66). Of all women with preterm birth and available ultrasound images, 15 % (7/48) had fibroid necrosis at the time of labour. These seven patients, supplemented with three patients with fibroid necrosis during their first pregnancy and at least one episode of imminent preterm birth, are described in more detail. In these ten patients, the fibroids increased substantially in size during the first and second trimester, leading to severe abdominal pain in all patients and hospital admission in seven patients. Ultrasound examination of the fibroids showed heterogenic changes and focal transonic areas in the fibroid, which are characteristics that indicate fibroid necrosis. In four patients, myomectomy was performed and necrosis was confirmed histologically. CONCLUSION: Fibroid necrosis during pregnancy is likely associated with (imminent) preterm birth. Clinicians are advised to structurally evaluate the myometrium in pregnancy, specifically in women presenting with abdominal pain in the second trimester.

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.

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.

Leiomyoma - Ciliary Body Tumor. A Case Report.

AIM: To demonstrate a rare case of ciliary body leiomyoma in our patient Case report: A 72-year-old female reported to our clinic for a preventive examination, upon which we found a dome-shaped grey-brownish mass on the retinal periphery. After completing gonioscopic and ultrasound examinations, we referred the patient to a specialist facility. Due to a finding of suspicious malignant melanoma, we completed the MRI scan and recommended enucleation of the eyeball. A histopathological examination showed a leiomyoma of the ciliary body. CONCLUSION: The aim of this case report is to demonstrate the difficulty of intraocular leiomyoma diagnosis. Only immunohistochemical examination differentiated the tumor from malignant melanoma and determined the diagnosis of ciliary body leiomyoma. Perhaps because of the extreme rarity of this type of tumor, we often neglect to consider a diagnosis of leiomyoma.

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.

Vulvar leiomyoma. / Leiomyom i vulva.

Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts, fibromas, fibroadenomas, lipomas and hamartomas. Adenoma was the tentative diagnosis is this case history, but the histology showed a benign leiomyoma.

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.

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.

Peritumoral stroma and systemic inflammatory response in cervical cancer.

OBJECTIVE: To compare cervical stroma in advanced cervical cancer with the control group; to compare, in the pre-treatment period, hemogram parameters in patients with advanced cervical cancer with the same parameters as the control group; and to verify if there is an association of stromal markers with prognostic factors in cervical cancer. MATERIALS AND METHODS: We prospectively evaluated 16 patients diagnosed with advanced invasive cervical cancer. A control group of 22 patients was used (uterine leiomyoma). Immunohistochemistry was performed to verify the stromal immunostaining of alpha-smooth muscle actin (SMA) and fibroblast activation protein alpha (FAP). Immunostainings and hemogram parameters were compared using Fisher's exact and Mann-Whitney Test, respectively. RESULTS: Strong FAP immunostaining was more frequent in patients with cervical cancer when compared with patients with leiomyoma (P = 0.0002). Regarding SMA, strong immunostaining was also found more in the group of cancer patients compared to the control group (P < 0.00001). The neutrophil-lymphocyte ratio (NLR) values were higher in the cancer patient group compared to the control group (P = 0.0019). There was no association of the parameters studied with prognostic factors. CONCLUSIONS: Strong FAP and SMA immunostaining was found more in patients with cervical cancer when compared to the control group. NLR values were also higher in cervical cancer.

Endoscopic Ultrasound-Guided Tissue Acquisition Using Fork-Tip Needle for Subepithelial Lesions: A Single-Center Validation Study.

BACKGROUND: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm). AIM: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle. METHODS: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests. RESULTS: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred. CONCLUSIONS: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.

A urethral leiomyoma presenting with dysuria: A rare case report.

RATIONALE: Leiomyoma is a benign smooth muscle tumor which is rarely found in urethra. We hereby report a case of a 44-year-old female who presented with complaints of dysuria. PATIENT CONCERNS: A 44-year-old female patient presented to the urology outpatient clinic with symptoms of dysuria. The patient described the presence of a protrusion from the urethra during urination. DIAGNOSIS: Urethral leiomyoma. INTERVENTIONS: Physical examination confirmed a solid urethral mass. CT scan and USG reports indicated that the mass originated from the mid-urethra with vascularity at the base. We performed a complete resection of the urethral mass. The patient was discharged after 3 days of observation. OUTCOME: During a follow-up after 1 month, the patient reported improved urinary flow and no occurrence of hematuria. The patient recovered well after discharge. LESSON: Urethral leiomyoma is a rare benign tumor that is often misdiagnosed in clinical practice. Diagnosis requires careful clinical examination. Surgical removal usually works well. It is important to remember that in some cases of acute urinary retention, it can be caused by a complete obstruction of a mass in the urethra. Urologists should be more cautious and experienced in handling such cases.

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report.

BACKGROUND: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. CASE PRESENTATION: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. CONCLUSIONS: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

Primary omental smooth muscle tumor in an adult male: a diagnostic dilemma for leiomyoma: a case report.

BACKGROUND: The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient. CASE PRESENTATION: A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up. DISCUSSION AND CONCLUSION: We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research.

Giant uterine tumor and miscarriage: how to proceed?

Expanding uterine masses can be the cause of pregnancy loss and add technical difficulties to uterus evacuation due to the intense anatomical distortion of the endocervical canal and uterine cavity. The literature is scarce in the peculiarities of the management of missed abortions in uterus with important distorted anatomies. We report a case of a primigravida patient who presented a rapid and expressive increase of abdominal volume due to a giant uterine mass, evolving to miscarriage. Ultrasound can be a useful tool, allowing visualization of the endocervical path and uterine cavity, helping to perform uterine evacuation in the presence of anatomical distortion without compromising the reproductive future. To the best of our knowledge, no such case has been previously reported.

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.