The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma.

OBJECTIVE: To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. METHODS: The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. RESULTS: The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. CONCLUSION: Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.

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.

Cytological features of a complete hydatidiform mole in a cervicovaginal smear: A case report.

Exfoliated trophoblastic cells can be seen in a cervicovaginal smear in cases of normal pregnancy or gestational trophoblastic disease (GTD) and can mimic high-grade squamous intraepithelial lesion (HSIL) or malignancy. Although they appear highly anaplastic, cytological features such as high nuclear to cytoplasmic ratio, irregular nuclear contours and scanty basophilic cytoplasm admixed with cytologically benign squamoid and endocervical cells can aid in differentiating them from malignant cells. We present a case of a 37-year-old woman with abnormal uterine bleeding for 3-months. There was no history of recent pregnancy or previous GTD. Her cervicovaginal smear showed a hypercellular smear exhibiting cytologically benign superficial and intermediate squamous cells along with clusters of benign endocervical cells with interspersed mononucleate cells. These mononucleate cells were large, with a hyperchromatic, pleomorphic nuclei, and scant basophilic cytoplasm. Cytological features were suggestive of trophoblastic cells and workup for pregnancy and GTD was advised. Her laboratory investigations showed markedly raised levels of ß human chorionic gonadotropins (ß-HCG) and ultrasound showed a uterine mass with snowstorm appearance. A uterine evacuation was performed after which histopathological examination showed microscopic features consistent with a complete hydatidiform mole. The rare presence of trophoblastic cells in a cervicovaginal smear can easily be confused with malignant cells and can be misleading to the pathologist. Trophoblastic cells should always be kept in mind when evaluating a cytology smear of a young patient irrespective of gestational status.

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.

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.

Placental site trophoblastic tumour: five challenges of patient clinical management.

Placental site trophoblastic tumour is a rare form of gestational trophoblastic disease accounting for about 1%-2% of all trophoblastic tumours. Diagnosis and management of placental site trophoblastic tumour can be difficult.We report a case of a 30-year-old woman diagnosed with a placental site trophoblastic tumour and identify the challenges in diagnosis and treatment of this rare situation. The presenting sign was abnormal vaginal bleeding that started 3 months after delivery. Image exams revealed an enlarged uterus with a heterogeneous mass, with vesicular pattern, and the increased vascularisation serum human chorionic gonadotropin level was above normal range. The histological diagnosis was achieved through hysteroscopic biopsy. Staging exams revealed pulmonary micronodules. The patient was successfully treated with hysterectomy and chemotherapy. The latest follow-up (37 months after diagnosis) was uneventful, and the patient exhibited no signs of recurrence or metastasis.

Opposing effects of thyroid hormones on cancer risk: a population-based study.

OBJECTIVE: The association between dysregulated thyroid hormone function and cancer risk is inconclusive, especially among different age groups and uncommon malignancies. We sought to determine the relation of TSH and free T4 levels with overall cancer risk as well as risk of specific cancer types. DESIGN AND METHODS: Data on thyroid hormone profile was collected from 375 635 Israeli patients with no prior history of cancer. Cancer cases were identified via the Israel National Cancer Registry. Cox proportional hazards model was used to assess hazard ratios for overall cancer as well as 20 cancer subgroups. RESULTS: In this study, 23 808 cases of cancer were detected over median follow up of 10.9 years. Among patients younger than 50 at inclusion, TSH in the hyperthyroid range, elevated free T4 and subclinical hyperthyroidism were associated with increased cancer risk (HR: 1.3, 1.28 and 1.31, respectively). In contrast, patients 50 or older with clinical hyperthyroidism were at lower cancer risk (HR: 0.64). Elevated TSH was associated with decreased risk of prostate cancer (HR: 0.67). Log-TSH elevation was associated with decreased risk of thyroid cancer (HR: 0.82) and increased risk of melanoma (HR: 1.11) and uterine cancer (HR: 1.27). Elevated free T4 was associated with increased lung cancer risk (HR: 1.54), while free T4 levels above the normal range and clinical hyperthyroidism were related to lower colorectal cancer risk (HR: 0.59 and 0.08, respectively). CONCLUSIONS: Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.

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.

Immune cell composition in the endometrium of patients with a complete molar pregnancy: Effects on outcome.

OBJECTIVE: In 15% of patients with complete hydatidiform mole (CHM), disease progresses to post-molar gestational trophoblastic neoplasia (GTN) after curettage. Tumor infiltrating lymphocytes (TILs) are essential in overcoming disease in many tumors. Infiltrating lymphocyte composition and density may influence trophoblast regression and development of post-molar GTN. We analyzed immune cell composition and density in curettaged endometrium of patients with CHM which spontaneously regressed, and of patients with CHM which progressed to post-molar GTN. METHODS: Sixteen patients with CHM and spontaneous regression, and 16 patients with CHM which progressed to post-molar GTN were selected. Immune cell composition and density of natural killer (NK) cells, natural killer T (NKT)-like cells, Cytotoxic T cells, T-Regulatory and T-Helper cells, were determined by multiplex immunohistochemistry (mIHC). RESULTS: Curettaged endometrium of patients with CHM and spontaneous regression contained a slightly higher number of immune cells compared to patients with CHM which progressed to post-molar GTN. NKT-like cell density was significantly higher in patients with spontaneous regression compared to patients with CHM which progressed to post-molar GTN (483 ± 296 vs.295 ± 143 (mean ± SD), p = 0.03) respectively. NKT-like cell density in the spontaneous regression group was split in 'high' and 'low' (i.e. above and below the median number of NKT-like cells). In patients with high NKT-like cell density, hCG normalized earlier than in patients with low NKT-like cell density (9.5 weeks, (range 3.7-14) vs. 12.9 weeks, (range 8.6-17.9), p = 0.05). CONCLUSION: A high number of NKT-like cells in the endometrium of CHMs may contribute to spontaneous regression of molar trophoblast cells.

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.

Placental site trophoblastic tumour: the rarest subtype of gestational trophoblastic disease.

Placental site trophoblastic tumour (PSTT) is a very rare form of gestational trophoblastic disease that grows slowly, secretes low levels of beta-subunit of human chorionic gonadotropin (ß-hCG), presents late-onset metastatic potential and is resistant to several chemotherapy regimens. Here, we report a case of PSTT in a 36-year-old woman who presented with amenorrhea and persistently elevated serum level of ß-hCG after a miscarriage. Transvaginal ultrasound revealed a hypovascular ill-defined solid lesion of the uterine fundus and MRI showed a tumour infiltrating the external myometrium with discrete early enhancement and signal restriction on diffusion-weighted imaging. PSTT was suspected, and after endometrial biopsy by hysteroscopy and posterior hysterectomy, microscopic examination allowed the final diagnosis. The level of ß-hCG dropped significantly in about a month after surgical treatment. Due to the rarity of PSTT, reporting new cases is crucial to improve the diagnosis and managing of these patients.

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.

Detection of PIK3CA E545A mutation in circulating tumor DNA of a patient affected by uterine carcinosarcoma.

Uterine carcinosarcomas are biphasic neoplasms consisting of mixed epithelial and mesenchymal elements, representing less than 5% of all uterine malignancies. Carcinosarcomas are rare, although the most common cause of uterine cancer-specific death. Few information is available on the pathogenesis, and molecular characterization is poorly investigated. Consequently, the treatment has not changed over the last years and is far too being tailored, consisting of surgery and traditional chemotherapy and radiotherapy. Molecular characterization of liquid biopsy by circulating tumor DNA (ctDNA)/circulating cell-free DNA (ccfDNA) evaluation in a patient with uterine carcinosarcoma. Here, we describe a case report of an 83-year-old woman with carcinosarcomas, stage T3aN0M0. Cancer cells did not express estrogen nor progesterone receptors, while p53 and p16 were positive. Molecular characterization of ccfDNA and of ctDNA was performed by quantitative PCR, amplification-refractory mutation system technology. The presence of phosphatidylInositol-4,5-bisphosphate 3-Kinase catalytic subunit alpha p.E545A mutation was detected in plasma. This approach may suggest the use of liquid biopsy and the development of specific targeted therapy for precision personalized medicine even in rare carcinosarcomas.

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.