Alterations in lipid profile upon uterine fibroids and its recurrence.

Uterine fibroids (UF) is the most common (about 70% cases) type of gynecological disease, with the recurrence rate varying from 11 to 40%. Because UF has no distinct symptomatology and is often asymptomatic, the specific and sensitive diagnosis of UF as well as the assessment for the probability of UF recurrence pose considerable challenge. The aim of this study was to characterize alterations in the lipid profile of tissues associated with the first-time diagnosed UF and recurrent uterine fibroids (RUF) and to explore the potential of mass spectrometry (MS) lipidomics analysis of blood plasma samples for the sensitive and specific determination of UF and RUF with low invasiveness of analysis. MS analysis of lipid levels in the myometrium tissues, fibroids tissues and blood plasma samples was carried out on 66 patients, including 35 patients with first-time diagnosed UF and 31 patients with RUF. The control group consisted of 15 patients who underwent surgical treatment for the intrauterine septum. Fibroids and myometrium tissue samples were analyzed using direct MS approach. Blood plasma samples were analyzed using high performance liquid chromatography hyphened with mass spectrometry (HPLC/MS). MS data were processed by discriminant analysis with projection into latent structures (OPLS-DA). Significant differences were found between the first-time UF, RUF and control group in the levels of lipids involved in the metabolism of glycerophospholipids, sphingolipids, lipids with an ether bond, triglycerides and fatty acids. Significant differences between the control group and the groups with UF and RUF were found in the blood plasma levels of cholesterol esters, triacylglycerols, (lyso) phosphatidylcholines and sphingomyelins. Significant differences between the UF and RUF groups were found in the blood plasma levels of cholesterol esters, phosphotidylcholines, sphingomyelins and triacylglycerols. Diagnostic models based on the selected differential lipids using logistic regression showed sensitivity and specificity of 88% and 86% for the diagnosis of first-time UF and 95% and 79% for RUF, accordingly. This study confirms the involvement of lipids in the pathogenesis of uterine fibroids. A diagnostically significant panel of differential lipid species has been identified for the diagnosis of UF and RUF by low-invasive blood plasma analysis. The developed diagnostic models demonstrated high potential for clinical use and further research in this direction.

Secretome Profiling and Computational Biology of Human Leiomyoma Samples Unravel Molecular Signatures with Potential for Diagnostic and Therapeutic Interventions.

In recent years, significant advancements have been made in the way the complex proteome samples are compared but the ultimate goal of routine biomarker discovery has yet to be achieved. Based on reverse genetic strategy, our study involved the spotting of genes showing expressional variability in uterine leiomyoma females. Serum samples were taken from uterine leiomyomas subjects (n=6) and healthy control subjects (n=6) for proteomic studies. Additionally, leiomyoma tissue samples (n=25) and normal myometrium samples (n=25) were taken for validation studies. In this study, we profiled the proteomes of uterine leiomyoma patient's serum and healthy control, along with relative quantification using Nano LC-MS/MS analysis. A total of 146 proteins were reported to be significantly differentially expressed (P value less than 0.05) in case and control sample. Statistical analysis identified a number of molecular signatures distinguishing healthy from diseased serum. Among these, five proteins lumican, ficolin, MASP2, EMSY, and kallistatin were further chosen according to their function for validation. Kallistatin was downregulated while ficolin, MASP2, lumican, and EMSY were found to be upregulated in the diseased sample. The expression modulations in the identified genes were further validated in twenty-five cases. Interactions among the differentially expressed proteins were identified followed with network analysis. Network analysis emphasized important pathways that are highly deregulated in myoma, and functional significance of these pathways in the pathology of the disease was discussed. Comparative expression analysis reveals distinct molecular signatures and their probable role in diagnosis of the disease.

Preoperative MRI and LDH in women undergoing intra-abdominal surgery for fibroids: Effect on surgical route.

INTRODUCTION: Our institution implemented a preoperative protocol to identify high-risk cases for which power morcellation should be avoided. MATERIAL AND METHODS: In this retrospective cohort study, an institutional protocol requiring preoperative Magnetic Resonance Imaging with diffusion-weighted imaging and serum Lactate Dehydrogenase levels was implemented. Chart review was performed including all women who underwent intra-abdominal surgery for symptomatic fibroids from 4/23/2013 to 4/23/2015. RESULTS: A total of 1,085 women were included, 479 before and 606 after implementation of the Magnetic Resonance Imaging / Lactate Dehydrogenase protocol. The pre-protocol group had more post-menopausal women (4% vs. 2%, p = 0.022) and women using tamoxifen (2% vs. 0%, p = 0.022) than those in the post-protocol group, but baseline patient characteristics were otherwise similar between groups. Incidence of malignant pathological diagnoses did not change significantly over the time period in relation to protocol implementation. The rate of open surgery for both hysterectomy and myomectomy remained the same in the year preceding and the year following initiation of the protocol (open hysterectomy rate was 19% vs. 16% in pre- and post-protocol groups, respectively, P = 0.463, and open myomectomy rate was 10% vs. 9% rates in pre- and post-protocol groups, respectively, P = 0.776). There was a significant decrease in the use of power morcellation (66% in pre- and 50% in post-protocol cohorts, p<0.001) and an increased use of containment bags (1% in pre- and 19% in post-protocol cohort). When analyzing the subset of women who had abnormal Magnetic Resonance Imaging / and Lactate Dehydrogenase results, abnormal Magnetic Resonance Imaging results alone resulted in higher rates of open approach (65% for abnormal vs. 35% for normal). Similarly, a combination of abnormal Magnetic Resonance Imaging and Lactate Dehydrogenase tests resulted in higher rates of open approach (70% for abnormal and 17% for normal). Abnormal Lactate Dehydrogenase results alone did not influence route. CONCLUSIONS: Rates of MIS procedures were decreased for women with abnormal preoperative Magnetic Resonance Imaging results. False positive results appear to be one of the main drivers for the use of an open surgical route.

Vitamin D as a risk factor for the presence of asymptomatic uterine fibroids in premenopausal Han Chinese women.

OBJECTIVES: To investigate the relationship between vitamin D deficiency and the risk of asymptomatic uterine fibroids (UFs). DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): The present analysis recruited 133 asymptomatic patients with UFs and 80 normal control subjects from October 2017 to June 2020. Age matching created 61 pairs. INTERVENTION(S): Medical history, transvaginal or transabdominal genital ultrasound scan, blood sampling, and measurement of vitamin D concentrations. MAIN OUTCOME MEASURE(S): Evaluation of the impact of vitamin D level on the risk of newly diagnosed asymptomatic UFs in premenopausal Han Chinese women. RESULT(S): Vitamin D levels of UF-positive patients were lower than those of healthy control subjects in unmatched samples (12.1 ng/mL vs. 16.8 ng/mL) and in matched samples (11.4 vs. 17.5 ng/mL). Younger patients (≤40 years) had a lower vitamin D level than older subjects in healthy control group (15.1 ng/mL vs. 19.0 ng/mL). We did not observe any age-vitamin D interactive effect in unmatched samples. Multivariate logistic regression revealed that asymptomatic patients presented a lower level of vitamin D than did normal groups in both unmatched and matched sample. In addition, the optimal threshold vitamin D level for having asymptomatic UFs was 14.34 ng/mL. CONCLUSION(S): Vitamin D deficiency may be associated with increased risk of asymptomatic UFs in premenopausal Han Chinese women.

Evaluation of Biomarkers in Myoma Patients: A Prospective Study Investigating the Role of LDH, CA 125, and IGF-1 after Uterus-Preserving Surgical Therapy.

OBJECTIVE: Myomas are one of the most common tumors of the lower abdomen in women. At present, sonography and clinical examination are the prevalent diagnostic standards for these tumors, and no biomarkers have been established yet. The primary aim of this study was to determine if the surgical removal of myomas leads to a drop of lactate dehydrogenase (LDH), CA 125, and/or insulin-like growth factor (IGF-1) and therefore if these parameters are suitable as potential biomarkers for the presence or recurrence of a myoma. STUDY DESIGN: The blood levels of LDH, CA 125, and IGF-1 were determined in 83 patients (age 18-50) with a verified diagnosis of myomas and surgical therapy at 3 different timepoints: preoperative (T0), 2 days postoperative (T1), and 6 months postoperative (T2). Vaginal sonography was performed preoperatively and once again at 6 months postoperatively. RESULTS: The median (Q1-Q3) LDH values dropped significantly postoperatively: 239 (217-266) U/L at T0 versus 217 (190-255) U/L at T1, p < 0.001. The median (Q1-Q3) IGF-1 values also dropped: 140.4 (118.6-179.0) ng/mL versus 112.4 (99.5-143.0), p < 0.001. By contrast, the CA 125 values rose slightly but not significantly. At 6 months (n = 34), the LDH values were not significantly different from either the preoperative or the immediate postoperative values. This was observed both in patients with and without a recurrence of myoma. In contrast, the median (Q1-Q3) IGF-1 level at T2 was significantly elevated both in patients with sonographic evidence of new myomas (129.0 [116.0-163.1] ng/mL, p = 0.023) and in patients with sonographic proof of no new myomas (161.0 [130.2-198.5] ng/mL, p < 0.001). CONCLUSION: Both LDH and IGF-1 dropped significantly in the immediate postoperative days in women with myomas after uterus-preserving surgeries were performed. The postoperative concentration of IGF-1 was correlated with the evidence of new myomas and can be potentially used for further monitoring. Future studies should be able to confirm these results. This study concludes that myomas do influence LDH and IGF-1 and could possibly be suitable as biomarkers.

The Significance of Measuring Vitamin D Serum Levels in Women with Uterine Fibroids.

Uterine fibroids (UFs) are benign tumors originating from smooth muscle cells and are considered a common pathology that affects numerous women which is a notable socio-economic problem. Several UF risk factors have been identified including black race, obesity, and vitamin D deficiency. Vitamin D is steroid compound with pleiotropic effects on the human body. Vitamin D deficiency is a major public health concern worldwide. Several studies have shown that the majority of UF patients experienced hypovitaminosis D. In addition, sufficient vitamin D serum levels are associated with the reduced risk of UFs. In this review, we present available data highlighting the importance of measuring vitamin D serum levels in women with UFs and women at a high risk for UF development. We proposed a preliminary clinical instruction of 25-hydroxyvitamin D measurements and vitamin D supplementation for clinicians who are involved in the treatment of patients with UFs. Achieving sufficient serum levels of vitamin D might be of interest in patients with UFs. Screening, supplementation, treatment guidelines, and public health strategies for vitamin D deficiency in women with UFs as well as women at a high risk of UF development might be of potential importance as well.

Benign leiomyoma with multiple metastases to vertebrae and calvarium: An index case with comprehensive review of endocrine targets.

"Benign" metastatic leiomyomas (BML) are indolently growing metastatic tumors which mostly associate with uterine leiomyomas in women in reproductive ages. The reason to define these lesions as "benign" despite metastasis is their pathological features with low mitotic counts, lack of or minimal nuclear atypia, pseudocyst formation, and coagulative necrosis unlike leiomyosarcomas. Despite lack of pathological malignant features, they may cause significant morbidity and even mortality. Here, we describe a BML case with metastases to vertebrae and skull bones. Vertebral and skull metastases of BMLs were very rarely reported. In treatment of these tumors, hysterectomy and GnRH modifier treatments are widely employed. GnRH agonists act by desensitization and downregulation of the GnRH receptors, while GnRH antagonists act via the canonical competitive blockage. These treatments reduce FSH and LH levels, thereby reducing the systemic levels of sex steroids which stimulate leiomyoma growth. However, leiomyomas inherently harbor aromatase activity and synthesize their own estrogen; hence, treatment with systemic estrogen antagonists may provide better tumor control. Another important factor in BML pathogenesis is progesterone, and both progesterone receptor antagonists and high-dose progesterone receptor agonists may reduce BML growth. Following surgical treatment of the calvarial mass and radiotherapy of the vertebral metastatic foci, our BML case was successfully managed with hysterectomy and anastrozole treatment. Higher awareness of BML cases and their molecular endocrinological features in the neurosurgical community may pave to develop better strategies for treatment of these tumors causing high morbidity.

Specificity of the lactate dehydrogenase isoenzyme index as a preoperative screen for uterine sarcoma before myomectomy.

OBJECTIVE: To evaluate the applicability of the Uterine mass Magna Graecia (UMG) risk index (elevation defined by a lactate dehydrogenase isoenzyme index >29) in women undergoing surgery for benign fibroids and to determine whether other factors were associated with an elevated index. An elevated UMG index has been reported to be associated with an increased risk of uterine sarcoma in Italian women. DESIGN: Retrospective cohort study. SETTING: University fibroid center. PATIENTS: All women presenting from July 1, 2013, through June 30, 2019, with fibroids who had lactate dehydrogenase isoenzymes collected and surgery performed. INTERVENTIONS: Calculation of UMG index. MAIN OUTCOME MEASURE: Applicability of UMG index. RESULTS: Of 272 patients initially identified, 179 met inclusion criteria, 163 with UMG index ≤29 and 16 with UMG index >29. There were no cases of uterine sarcoma. Race, age, and presence of endometriosis, adenomyosis, or degenerating fibroids were not predictors of elevated UMG index. Body mass index (BMI) was positively associated with elevated UMG index. Specificity of UMG index to exclude uterine sarcoma was 91.1% (163/179) and higher in non-obese (BMI<30; 95.1%) than obese women (85.5%). CONCLUSION: A previously reported UMG index cutoff of 29 had a specificity of 91.1% (higher with normal BMI and lower when obese) in our patient population. Although lower than previously reported, the index could be a useful initial method of preoperative screening of women with symptomatic fibroids. Higher BMI appears to be associated with elevated UMG indices, increasing the false-positive rate in obese women.

Impact of a Blood Conservation Bundle Checklist on Perioperative Transfusion Rates during Myomectomy.

STUDY OBJECTIVE: The primary objective was to introduce an intraoperative blood conservation bundle (BCB) checklist into clinical practice and assess its impact on perioperative blood transfusion rates during myomectomy. DESIGN: Prospective cohort study with retrospective control group. SETTING: A Canadian tertiary-care teaching hospital. PATIENTS: One hundred and eighty-six women who underwent myomectomy. INTERVENTIONS: The BCB is a physical checklist attached to the patient chart and consists of evidence-based medical and surgical interventions to reduce intraoperative blood loss. It was introduced in October 2018, and data were collected prospectively during a 12-month period for all open, robotic, and laparoscopic myomectomies at our institution. The primary outcome was the perioperative transfusion rate, and the secondary outcomes included estimated intraoperative blood loss, perioperative complications, readmissions, and BCB usage rates. Data were compared with those of a historic control group for a 24-month period before the BCB introduction. MEASUREMENTS AND MAIN RESULTS: In the pre-BCB period, 134 myomectomies (90 open, 31 robotic, and 13 laparoscopic) were performed, and during our study period, 52 myomectomies (33 open, 10 robotic, and 9 laparoscopic) were performed. There was a decrease in transfusion rate from 15.7% (21/134) to 7.7% (4/52) after introduction of the BCB; however, this was not significant (p = .152). The mean estimated blood loss was lower postintervention (491 mL ± 440 mL vs 350 mL ± 255 mL; p <.05) as was the mean delta hemoglobin (-28 g/L ± 13.0 g/L vs -23 g/L ± 11.4g/L; p <.05]. The checklist was used in 92.3% of cases (48/52). There were no differences in intraoperative or postoperative complications or readmission rates. CONCLUSION: Best practice care bundles can improve knowledge translation of guidelines into care delivery. The introduction of the BCB was successful in reducing intraoperative blood loss during myomectomy at our institution. The BCB is a simple, effective tool that can be easily adopted by gynecologic surgeons to guide intraoperative decision-making during myomectomy.

Serum transforming growth factor ß and leucine-rich α-2-glycoprotein 1 as potential biomarkers for diagnosis of uterine leiomyomas.

BACKGROUND AND AIM: Transforming growth factor ß (TGF-ß) and leucine-rich α-2-glycoprotein 1 (LRG1) play significant roles in the pathogenicity of uterine leiomyomas (ULMs). The current study aimed to assess the diagnostic values of serum TGF-ß and LRG1 in terms of the presence and severity of ULMs. METHODS: Premenopausal women with ULMs (n=44) together with age-adjusted ULM-free individuals (n=41) were incorporated into the study. ULMs were detected and evaluated using transvaginal ultrasonography. Serum levels of TGF-ß and LRG1 were quantified by enzyme-linked immunosorbent assay. RESULTS: Mean concentrations of serum TGF-ß and LRG1 were significantly higher in the group of patients with ULMs compared to the control group (p<0.05). The volume of the largest leiomyoma was positively correlated with the levels of TGF-ß (r = 0.414, p= 0.005) and LRG1 (r = 0.341, p= 0.023). The receiver-operating characteristics analysis demonstrated moderate and robust values of area under the curve for TGF-ß (0.755) and LRG1 (0.90), respectively. CONCLUSION: Increases in serum levels of TGF-ß and LRG1 is associated with the incidence and severity of ULMs. LRG1 in particular but also TGF-ß may be able to serve as reliable biomarkers for the diagnosis and monitoring of ULMs.

Proinflammatory mediators and reproductive failure in women with uterine fibroids.

OBJECTIVE: study the levels of proinflammatory mediators and their correlation with reproductivefailure in women with uterine fibroids (UF). MATERIALS AND METHODS: 90 women aged 18 - 45 years (mean age - 33.9 ± 0.31) were recruited in the study: 60 women with UF were included in the study group and 30 healthy women were included in the control group. The lymphocyte count was performed with laser-based flow cytofluorimetry. The levels of C-reactive protein (CRP), interferon IFN-ß (IFN-ß), interferon-γ (IFN-γ), tumor necrotizing factor α (TNF-α) and basic fibroblast growth factor (FGF basic) were detected with ELISA test. The diagnosis of UF was confirmed with histological examination of biopsy specimen. RESULTS: Typical clinical features of UF (abnormal uterine bleeding, pelvic pains, symptoms of adjacent organs compression) were found in 66.67% women in the study group while 18.33% of them had miscarriages and 26.67% had infertility. Women with UF had significantly higher absolute count of lymphocytes: CD3+, CD19+, CD16+CD56+, CD4+, CD8+, CD95+CD3+, proinflammatory mediators: TNF-α, IFN-ß, CRP, FGF basic and decreased levels of IFN-γ compared with the control group. CONCLUSION: In women of reproductive age, typical symptoms of UF are associated with reproductive failure with activation of adaptive immunity, angiogenic factors, inflammatory cell reactions, deficit of human antitumor factors, that is why detection of TNF-α, СРБ, IFN-γ in serum is necessary to perform in pregravid preparation of women, including IVF program.

Use of GnRH analogues in the reduction of submucous fibroid for surgical hysteroscopy: A systematic review and meta-analysis / Uso de análogo de GnRH na redução de mioma submucoso na histeroscopia cirúrgica: Revisão sistemática e meta-análise

Abstract Objective Gonadotropin-releasing hormone analogues (GnRH-a) have been used preoperatively before hysteroscopic myomectomy to decrease the size and vascularization of the myomas, but evidence to support this practice is weak. Our objective was to analyze the use of GnRH-a in the reduction of submucous fibroid as a facilitator for surgical hysteroscopy from published clinical trials. Data sources Studies from electronic databases (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), published between 1980 and December 2018. The keywords used were fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection and their correspondents in Portuguese. Study selection The inclusion criteria were controlled trials that evaluated the GnRH-a treatment before hysteroscopic resection of submucous myomas. Four clinical trials were included in the meta-analysis. Data collection Two review authors extracted the data without modification of the original data, using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third person. Data synthesis The present meta-analysis included a total of 213 women and showed no statistically significant differences in the use of GnRH-a compared with the control group for complete resection of submucous myoma (relative risk [RR]: 0.94; 95%; confidence interval [CI]: 0.80-1.11); operative time (mean difference [MD]: - 3.81; 95%;CI : - 3.81-2.13); fluid absorption (MD: - 65.90; 95%;CI: - 9.75-2.13); or complications (RR 0.92; 95%;CI: 0.18-4.82). Conclusion The present review did not support the routine preoperative use of GnRH-a prior to hysteroscopic myomectomy. However, it is not possible to determine its inferiority when compared with the other methods due to the heterogeneity of existing studies and the small sample size.

Resumo Objetivo Análogos de hormônio liberador de gonadotrofina (GnRH-a) têm sido usados no pré-operatório de miomectomia histeroscópica para reduzir o tamanho e vascularização dos miomas, mas a evidência que suporta essa prática é fraca. Nosso objetivo foi analisar o uso de GnRH-a na redução do mioma submucoso como um facilitador de histeroscopia cirúrgica em ensaios clínicos publicados. Fonte de dados Estudos de bases de dados eletrônicas (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), publicados entre 1980 e dezembro de 2018. As palavras-chave usadas foram fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection e seus correspondentes em português. Seleção dos estudos Os critérios de inclusão foram ensaios clínicos controlados que avaliaram o tratamento com GnRH-a antes da ressecção histeroscópica de miomas submucosos. Quatro ensaios clínicos foram incluídos na meta-análise Coleta de dados Dois autores revisores extraíram os dados, sem modificarem os dados originais, usando a forma acordada. Nós resolvemos as discrepâncias através de discussão ou, se necessário, consultando um terceiro autor. Síntese dos dados A meta-análise incluiu um total de 213 mulheres e não demonstrou diferença estatisticamente significativa no uso de GnRH-a comparado com o grupo controle para ressecção completa de mioma submucoso (risco relativo [RR]: 0.94. índice de confiança [IC] 95%;: 0.80-1.11); tempo cirúrgico (diferença de média [MD]: - 3.81; IC95%;: -3.81-2.13); absorção de fluidos (MD: - 65.90; IC95%;: - 9.75-2.13); ou complicações (RR 0.92; IC95%;: 0.18-4.82). Conclusão A presente revisão sistemática não suporta o uso pré-operatório rotineiro de GnRH-a antes de miomectomia histeroscópica. No entanto, não é possível determinar sua inferioridade quando comparado aos outros métodos devido à heterogeneidade dos estudos existentes e ao pequeno tamanho da amostra.

Correlation of low serum vitamin-D with uterine leiomyoma: a systematic review and meta-analysis.

BACKGROUND: There is a growing body of evidence on low serum vitamin-D levels and the risk of uterine leiomyomas (UL). Therefore, this systematic review and meta-analysis was conducted to investigate the association between serum vitamin D levels and UL occurrence. METHODS: Searches were systematically conducted of the electronic databases PubMed, Scopus, EMBASE, Web of Science (ISI), Cochrane library, Ovid, and Google Scholar to identify relevant studies from inception until February 6, 2020. Heterogeneity across the included studies was examined using Cochran's Q and I-square (I2). Data was pooled using random effects modeling and expressed as standardized mean differences (SMDs). RESULTS: Nine eligible studies with a total of 1730 participants (835 patients with UL and 895 controls) were included in the current meta-analysis. Pooled results with random effects modeling indicated that serum vitamin D levels were significantly lower in patients with UL than in the control group (n = 9, SMD = - 0.67; 95% CI, - 0.98, - 0.35, p < 0.001; I2 = 89.3%, p < 0.001). Based on the findings of subgroup analyses, it was found that the SMD values across the included studies from Asia (n = 4, SMD = - 1.20; 95% CI, - 1.45, - 0.96, p < 0.001; I2 = 30.6%, p = 0.229) were lower than those from Europe (n = 3, SMD = - 0.34; 95% CI, - 0.49, - 0.18, p < 0.001; I2 = 0.0%, p = 0.602) and Africa (n = 2, SMD = - 0.13; 95% CI, - 0.29, 0.04, p = 0.128; I2 = 0.0%, p = 0.417), although the difference was not significant in Africa. Publication year was also found to be a potential contributor's variable in the pooled SMD using the meta-regression method (t = - 3.00, p = 0.02). CONCLUSIONS: To the best of our knowledge, the current meta-analysis showed for the first time that serum vitamin D levels were significantly lower in women with UL in selected populations.

Dietary fat intake, erythrocyte fatty acids, and risk of uterine fibroids.

OBJECTIVE: To prospectively evaluate the association between dietary fat intake and risk of uterine fibroids; and to evaluate the association between erythrocyte membrane fatty acid (FA) levels and fibroid risk. DESIGN: Prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence interval (CI). In a subset of participants 34 individual FAs were measured and logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI for the association between FA tertiles and fibroids. SETTING: Not applicable. PATIENT(S): Premenopausal US women (81,590) in the Nurses' Health Study II, aged 25-42 years at enrollment in 1989 for whom diet was assessed by a food frequency questionnaire. A total of 553 participants with erythrocyte FA measurements. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cases of fibroids were defined on the basis of self-reported ultrasound or hysterectomy confirmation. RESULT(S): A total of 8,142 cases of ultrasound-confirmed or hysterectomy-confirmed were diagnosed during an 18-year period (1991-2009). No associations were observed between intake of any dietary fats and fibroids in the multivariable models. However, when erythrocyte FAs were examined, an inverse association was observed between total n-3 polyunsaturated FAs and likelihood of fibroids (OR for third versus first tertile, 0.41; 95% CI 0.19-0.89). In addition, total trans FAs were associated with more odds of fibroids (OR for third tertile, 3.33; 95% CI 1.50-7.38). CONCLUSION(S): Our findings provide preliminary suggestions that n-3 polyunsaturated FAs and trans FAs may play a role in fibroid etiology; however, these results should be confirmed in future studies.

Preoperative clinical characteristics scoring system for differentiating uterine leiomyosarcoma from fibroid.

BACKGROUND: Morcellation may lead to intraperitoneal spread of tumor cells, thus making prognosis of undiagnosed uterine leiomyosarcoma (ULMS) worse. However, preoperative diagnosis of ULMS remains challenging. This study aimed to design a preoperative clinical characteristics scoring system for differentiating ULMS from uterine fibroid. METHODS: This study enrolled 45 ULMS patients and 180 uterine fibroid patients in Peking Union Medical College Hospital from January 2013 to December 2018. RESULTS: The incidence of occult ULMS was 0.59% (95% CI, 0.39-0.71%). Age ≥ 40 years old (OR 2.826, 95%CI 1.326-5.461), tumor size ≥7 cm (OR 6.930, 95% CI 2.872-16.724), neutrophil-to-lymphocyte ratio (NLR) ≥ 2.8 (OR 3.032, 95%CI 1.288-7.13), number of platelet ≥298 × 109/L (OR 3.688, 95%CI 1.452-9.266) and lactate dehydrogenase (LDH) ≥ 193 U/L (OR 6.479, 95%CI 2.658-15.792) were independent predictors of ULMS. A preoperative clinical characteristics scoring system was designed based on OR values, with a total score of 7 points. Tumor size ≥7 cm, LDH ≥ 193 U/L were assigned 2 points, while age ≥ 40 years old, NLR ≥ 2.8 and number of platelet ≥298 × 109/L were assigned 1 point. Score ≥ 4 points was a useful predictor in diagnosing ULMS from fibroid (sensitivity 0.800, specificity 0.778). CONCLUSIONS: The incidence of occult ULMS was low. Age ≥ 40 years old, tumor size ≥7 cm, LDH ≥ 193 U/L, NLR ≥ 2.8 and number of platelet ≥298 × 109/L were independent predictors of ULMS. The preoperative clinical characteristics scoring system could be helpful in preoperative diagnosis of occult ULMS.

Critically High Carboxyhemoglobin Level following Extensive Hysteroscopic Myomectomy.

Studies have demonstrated that during hysteroscopic myomectomy with bipolar diathermy, carbon monoxide is produced and enters the patient's circulation. However, little is known regarding the immediate or long-term sequelae of transient rises in carboxyhemoglobin levels during hysteroscopic surgery. This paper aims to suggest recommendations for acute evaluation, management, patient counseling, and future research. We present a case of a 36-year-old woman (Gravida 0, Para 0) with abnormal uterine bleeding-leiomyoma and resultant anemia, undergoing hysteroscopic resection of a large submucous myoma. During surgery, the patient was found to have a critically elevated level of carboxyhemoglobin and accompanying electrocardiogram derangements. She was managed with prolonged intubation, 100% O2, and trending of her carboxyhemoglobin levels before extubation. This demonstrates the importance of being cognizant of the potentially toxic gaseous byproducts of bipolar resection and of including intravasation of these byproducts in one's consideration of patient safety during extensive resections. Bipolar hysteroscopic resection of large leiomyomas may result in critically high carboxyhemoglobin levels, which can impair end-organ oxygen delivery with resultant ischemia; the risks of myocardial ischemia should be discussed with the anesthesia team before attempting an extensive resection. Electrocardiogram changes indicative of ischemia should prompt discontinuation of the case. Finally, carboxyhemoglobin poisoning should be included in the differential diagnosis of patients who demonstrate longer-than-expected anesthesia recovery times after bipolar resection of large submucous leiomyomas, and they should be managed with repeat evaluation of carboxyhemoglobin levels, supplemental oxygen, and cardiac monitoring.

Development of a novel and rapid measurement system for growth differentiation factor-15, progranulin, and osteopontin in uterine sarcoma.

Uterine sarcomas are rare and aggressive gynecologic tumors with poor prognosis; therefore, early diagnosis is crucial for therapy. However, it is very difficult to distinguish uterine sarcomas from leiomyomas which are common benign uterine tumors. Therefore, the development of a diagnostic method that utilizes reliable biomarkers to distinguish uterine sarcomas from leiomyomas is important so as to identify the rare tumors. The candidate factors as novel biomarkers were searched for in public databases and a pilot study was performed for confirmation. Growth differentiation factor-15 (GDF15), progranulin, and osteopontin were identified as candidate biomarkers for diagnosing uterine sarcoma. Thus, developing a rapid and easy method to measure these factors could help establish a screening system for uterine sarcomas. In this study, we developed a novel measurement system for these factors using a compact chemical luminescence immunological automatic analyzer POCubeTM. This assay system, which is based on the flow-through membrane immunoassay, completes the whole process and generates results within 15 min. Serum concentrations of these factors measured via POCubeTM correlated well with those measured using enzyme-linked immunosorbent assay (r = 0.994 for GDF15, r = 0.992 for progranulin, and r = 0.976 for osteopontin). The POCubeTM system provides rapid and easy measurement of these factors, thereby facilitating uterine sarcoma diagnosis.

Evaluation of 25-hydroxy vitamin D3 levels in patients with a fibroid uterus.

A cross sectional study was done at Era's Lucknow Medical College & Hospital, Lucknowwith the objective to evaluate 25-hydroxyVitaminD3 level in women with and without uterine fibroid. Ninety subjects (45 cases and 45 controls) were enrolled. Cases were those having at least 1 uterine fibroid ≥10 mm detected on ultrasonography, while controls were those not having any uterine pathology. Estimation of Serum 25-hydroxyvitaminD3 Level was done. The mean ± SD concentration of 25-hydroxyvitaminD3 was Significantly lower in cases compared with controls (15.10 ± 6.09 vs 26.09 ± 7.90 respectively, p < 0.001).The number of women with 25-hydroxyvitaminD3 deficiency in cases and controls was 9(20%) and 3(6.67%) respectively (p < 0.001). Uterine fibroid size increased proportionately with decrease in 25-hydroxyvitaminD3 levels, (p = 0.014). We concluded that VitaminD3 deficiency is significantly associated with the occurrence of Uterine fibroids. Further studies need to be conducted in order to evaluate the therapeutic benefits VitaminD3 supplementation in the patients of Uterine fibroid.Impact Statementwhat is already known on this subject? Vitamin D is believed to regulate cell proliferation and differentiation, inhibit angiogenesis and stimulate apoptosis. Now a days hypovitaminosis D is believed to be a major risk factor in the development of uterine fibroids. There are several ideas about the use of vitamin D in uterine fibroid prevention or as a long term treatment but ongoing clinical trials in the area remain scarce.what do the results of this study add? Our study showed that 25-hydroxivitamin d3 deficiency is significantly associated with uterine fibroid.Lower levels of 25-hydroxivitamin d3were found to have aninverse relationship with increased size of fibroid uterus.what are the implications of these findings for clinical practice and / or further reasearch? Vitamin D seems to be a promising, safe and low-cost agent for the prevention and treatment of uterine fibroids. However, further studies with larger sample size are needed to confirm our findings.

Comparison of uterine fibroids' growth pattern during pregnancy according to fetal sex: an observational study.

BACKGROUND: To investigate the effect of fetal sex on fibroids' growth during pregnancy according to the hCG serum levels METHODS: Observational study conducted from January 2007 to December 2016 on women with ultrasound identification of uterine fibroids who had a pregnancy within 1 year from diagnosis. The fibroids diameter was determined during the pre-pregnancy ultrasound, early first trimester (5-7 weeks), late first trimester (11-13 weeks), second trimester (19-21 weeks), and third trimester (31-33 weeks). The diameter growth was calculated in each interval between two ultrasounds. The hCG serum levels were determined both in early and late first trimester. The correlation between hCG levels and fibroid diameter was evaluated. Obstetric outcomes collected were gestational weeks at birth and the rate of cesarean section. Neonatal outcomes were birthweight and Apgar score at 1 min. RESULTS: Eighty-seven of the included women had a male fetus, and 70 had a female fetus. A progressive increase of fibroid diameter was observed from pre-pregnancy to second trimester for both fetal sexes. In third trimester, the mean ± SD fibroid diameter of female fetuses showed a slowdown, while the mean ± SD fibroid diameter of male fetuses continued to grow. Women carrying a female fetus presented a higher fibroid diameter in early first trimester (33.5 ± 13.3 mm vs 27.4 ± 11.0 mm, p < 0.01), late first trimester (40.2 ± 13.9 mm vs 34.6 ± 11.7 mm, p < 0.01), and second trimester (40.5 ± 14.9 mm vs 34.7 ± 10.3 mm, p < 0.01). The hCG serum levels resulted higher in women with a female fetus: 61406 (50554-71760) mU/ml vs 46016 (37160-56744) mU/ml (p < 0.01). A positive correlation between hCG levels and fibroid diameter was found both for male and female fetuses (male r = 0.77, 95% CI 0.71-0.82, p < 0.01 and female r = 0.82, 95% CI 0.76-0.86, p < 0.01). CONCLUSION: Women with female fetus seem to have a higher growth of fibroids up to second trimester of pregnancy. This process may be mediated by the higher serum hCG levels found in women expecting a female fetus.