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

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

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.

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.

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.

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.

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.

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.

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.

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.

Circulating Transcripts and Biomarkers in Uterine Tumors: Is There a Predictive Role?

PURPOSE OF REVIEW: Uterine cancer comprises endometrial carcinoma and the uterine sarcoma. Endometrial carcinomas are the most frequent variant and have early symptoms and a solid diagnostic work up, resulting in a rather fair prognosis. However, in case of advanced stage disease and relapse, treatment options are limited and prognosis is impaired. Uterine sarcomas are rare, often lacking symptoms and no diagnostic tool for correct pre-operative diagnosis are available. Prognosis is poor. RECENT FINDINGS: Circulating biomarkers as a liquid biopsy could be beneficial as a diagnostic tool in uterine sarcomas. For both carcinomas and sarcomas, circulating biomarkers could be of use in predicting early disease recurrence. This review in endometrial carcinoma and uterine sarcoma focus on circulating biomarkers; such as proteins; circulating tumor cells; circulating tumor DNA; microRNA; and immune cells.

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.

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.

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.

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.

Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma.

Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.

Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.

BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Neutrophilia and mortality in women with uterine carcinosarcoma.

OBJECTIVE: The objective of this study was to investigate the relationship between pre-treatment absolute neutrophil count and clinical outcomes in patients with uterine carcinosarcoma. METHODS: In an Institutional Review Board approved, retrospective cohort study of 103 patients with uterine carcinosarcoma, the pre-treatment absolute neutrophil count data were obtained from the medical records, along with clinical, pathologic, treatment, and outcome data. Kaplan-Meier survival estimates were calculated and compared by the log rank test. Univariable and multivariable Cox proportional hazard regression models were used to examine the relationship of pre-treatment absolute neutrophil count with progression-free survival and overall survival. RESULTS: Uterine carcinosarcoma patients in the highest quartile of pre-treatment absolute neutrophil count had significantly reduced progression-free survival (p<0.001, log rank test), and overall survival (p<0.001, log rank test), compared with patients in the lower absolute neutrophil count quartiles. On multivariable analysis, high absolute neutrophil count was an independent poor prognostic factor for disease recurrence, HR 2.97 (95% CI 1.35 to 6.53, p=0.007) for highest versus lowest quartile absolute neutrophil count, and for mortality, HR 4.43 (95% CI 1.64 to 12.00, p= 0.003). CONCLUSIONS: High pre-treatment absolute neutrophil count is an independent poor prognostic factor in patients with uterine carcinosarcoma and may be useful as a potential biomarker in clinical trials. The mechanistic relationship of neutrophilia and uterine carcinosarcoma progression merits further investigation.

Spontaneous regression of quiescent gestational trophoblastic disease after pregnancy: a case report.

BACKGROUND: A persistent low-level elevation of serum human chorionic gonadotropin (hCG) without clinical or radiological evidence of pregnancy or tumors was recently defined as quiescent gestational trophoblastic disease (Q-GTD). Whether patients with Q-GTD should be treated or allowed to become pregnant remains unclear. We herein report a rare case of Q-GTD in which the hCG level spontaneously returned to normal after a successful pregnancy. CASE PRESENTATION: The patient was a 37-year-old primigravida who presented with a persistent low-level elevation of hCG after uterine evacuation of a hydatidiform mole. There was no evidence of neoplasia in the uterus or distant metastasis. The low-level elevation of hCG persisted for at least 2 years but never exceeded 200 mIU/mL. The patient had a successful pregnancy at the age of 40 years. CONCLUSIONS: Interestingly, her hCG level subsequently normalized without chemotherapy. The present case may imply the safety and therapeutic effect of pregnancy in women with Q-GTD.

Analysis of uterine corporeal mesenchymal tumors occurring after menopause.

OBJECTIVE: Because it is difficult to diagnose accurately whether uterine corporeal mesenchymal tumors are benign or malignant before surgery, an understanding of the characteristics of patients with uterine sarcomas occurring in the postmenopausal period is required. METHODS: We retrospectively reviewed the cases of women who underwent surgery for uterine mesenchymal tumors at our hospital. RESULTS: Among 487 operated cases, 447 tumors occurred in the premenopausal period and 40 occurred in the postmenopausal period. Uterine sarcomas were observed in 5 cases (1.1%) during the premenopausal period and in 11 cases (28%) during the postmenopausal period. Among the postmenopausal patients, age, age at menopause, body mass index (BMI), tumor size, incidence of abnormal vaginal bleeding, serum tumor marker levels (cancer antigen 125, carbohydrate antigen 19-9, and carcinoembryonic antigen), and serum lactate dehydrogenase values were not significantly different between patients with benign tumors and those with malignant tumors. On the other hand, the incidence to have abnormal signal on MRI was significantly higher in patients with malignant tumors than in patients with benign tumors. CONCLUSION: In our hospital, the incidence of malignant tumors in women with uterine corporeal mesenchymal tumors was much higher in postmenopausal patients than in premenopausal patients. Because it is generally not easy to diagnose uterine sarcomas before surgery, surgery should be positively considered when uterine sarcomas cannot be ruled out for patients in the postmenopausal period.

The potential value of red blood cell distribution width in patients with invasive hydatidiform mole.

BACKGROUND: Red blood cell distribution width (RDW) has attracted increasing attention in cancer. The aim of this study was to assess the changes of RDW in patients with invasive hydatidiform mole and analyze the relationship between RDW and invasive hydatidiform mole. METHODS: A retrospective analysis was performed on 102 patients diagnosed as invasive hydatidiform mole in the First Affiliated Hospital of Guangxi Medical University from January 2009 to March 2018. A total of 120 healthy subjects were used as a control group. The Mann-Whitney U test was used for comparison between the invasive hydatidiform mole and control groups. Comparison of RDW with other blood parameters was performed using Spearman's. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were also determined. RESULTS: The RDW, platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and absolute lymphocyte count were significantly elevated in the invasive hydatidiform mole group compared with control group. The hemoglobin (Hb) concentration, mean red blood cell volume (MCV) and platelet count (PLT) were significantly lower in invasive hydatidiform mole group than control group. Grade III and above invasive hydatidiform mole patients had higher levels of RDW than grade I and II patients. Correlation analysis showed that RDW was negatively correlated with Hb, MCV, NLR, and neutrophil count, but positively correlated with PDW and different stages of invasive hydatidiform mole. The ROC curve showed that the AUC of the RDW was 0.660 (95% CI 0.581-0.740; P < 0.01). CONCLUSION: This study reveals the potential value of RDW in invasive hydatidiform mole.