The Extremely-Low-Frequency Electromagnetic Field Affects Apoptosis and Oxidative-Stress-Related Genes and Proteins in the Porcine Endometrium-An In Vitro Study.

Nowadays, the extremely-low-frequency electromagnetic field (ELF-EMF) is recognized as environmental pollution. The data indicate that the ELF-EMF may affect factors related to epigenetic regulation and alter important biological processes in the uterus. The impact of the ELF-EMF on apoptosis and oxidative-stress-related genes has not been documented in porcine endometrium. This raises the question of whether the exposure to the ELF-EMF can induce apoptosis and/or oxidative stress in the endometrium of pigs during the peri-implantation period. Porcine endometrial slices (100 ± 5 mg) collected (n = 5) during the peri-implantation period were treated in vitro with ELF-EMF at a frequency of 50 Hz and flux density of 8 × 104 mG for 2 h. To determine the effect of ELF-EMF on apoptosis and oxidative stress in the endometrium, CASP3, CASP7, CIDEB, GADD45G, NOS1, NOS2, NOS3, and TP53I3 mRNA transcript were analyzed using real-time PCR, and protein abundance of CASP3, CASP7 using Western blot, and eNOS using ELISA were determined. Moreover, CASP3/7 and NOS activity was analyzed using flow cytometry and colorimetry, respectively. The decreased CASP7 and increased NOS3 mRNA transcript and protein abundance in ELF-EMF-treated endometrium were observed. Moreover, CIDEB, GADD45G, and TP53I3 mRNA transcript abundance was increased. Only p ≤ 0.05 was considered a statistically significant difference. The documented alterations indicate the potential of the ELF-EMF to affect apoptosis and generate oxidative stress in the endometrium. The insight into observed consequences documents for the first time the fact that the ELF-EMF may influence endometrial cell proliferation, angiogenesis, and/or tissue receptivity during peri-implantation.

Bio-modulated mice epithelial endometrial organoids by low-level laser therapy serves as an invitro model for endometrial regeneration.

Endometrial regeneration is a dynamic process that is not well understood. The destruction of the endometrium with the formation of intrauterine adhesions is known as Asherman's syndrome. The lesions range from minor to severe adhesions and their impact on pregnancy is well documented. Operative hysteroscopy is the mainstay of diagnosis and treatment of intrauterine adhesions. Nevertheless, the recurrence rates remain high. It was recorded that low-level laser therapy in low doses has a stimulatory effect on different tissues while the high dose produces a suppressive effect. Organoid is a three-dimensional assembly that displays architectures and functionalities similar to in vivo organs that are being developed from human or animal stem cells or organ-specific progenitors through a self-organization process. Our prospective was to study the effect of Low-Level Laser Therapy (LLLT) on mouse epithelial endometrial organoids regarding cell proliferation and endometrial regeneration as a new modality of treatment. An in vitro clinical trial to generate mouse epithelial organoid model and testing LLLT using He:Ne 632.8 nm device on organoids proliferation, function, and their response to ovarian hormones was performed. Trying endometrial regeneration by culturing organoids with decellularized uterine matrix (DUM) and studying the LLLT effect on the regeneration process. LLLT produced a proliferative effect on the epithelial mouse organoids confirmed by Ki67 and PCNA IHC. The organoids could regenerate the epithelial layer of the endometrium in vitro on DUM and LLLT could help in this process. In conclusion, organoids whether control or bio-stimulated proved a new modality to regenerate the endometrium.

Effects of electromagnetic field (EMF) radiation on androgen synthesis and release from the pig endometrium during the fetal peri-implantation period.

An electromagnetic field (EMF) may have effects on female reproduction. This study was conducted to determine whether EMF [50 and 120 Hz, 2 and 4 h of incubation in the presence or absence of progesterone (P4, 10-5 M)] affects androgen synthesis and release from the pig endometrium. Endometrial slices were collected from pigs (n = 5) during the fetal peri-implantation period (i.e., days 15-16 of gestation) and treated in vitro with EMF. The selected endometrial slices were treated with P4 to determine whether this hormone has effects on protection of the tissue from EMF radiation. The CYP17A1 and HSD3B1 mRNA transcript abundance, steroid 17αhydroxylase/17, 20-lyase (cytochrome P450c17) and hydroxyΔ5steroid dehydrogenase/3ß and steroidΔisomerase (3ßHSD) protein abundance were examined using Real-Time PCR and Western Blot procedures, respectively. In media collected after incubation, the concentrations of androstenedione (A4) and testosterone (T) were quantified used a RIA. When P4 was added to the culture medium, EMF radiation had suppressive effects on endometrial T release after 2 and 4 h of incubation when the EMF treatment was occurring and increased A4 release after 4 h of incubation with EMF at 120 Hz. When there was no inclusion of P4, release of A4 was decreased after 2 h of EMF treatment at 120 Hz and after 4 h of EMF treatment at 50 and 120 Hz. Progesterone did not have functions that protected the pig endometrium against EMF radiation during the fetal peri-implantation period.

Effect of surgical approach on risk of recurrence after vaginal brachytherapy in early-stage high-intermediate risk endometrial cancer.

OBJECTIVE: The objective was to determine if surgical approach affects time to recurrence in early-stage high-intermediate risk endometrial cancer (HIR-EC) treated with adjuvant vaginal brachytherapy (VBT). METHODS: In this retrospective cohort study, HIR-EC patients treated with VBT between 2005 and 2017 were identified and those who received open or minimally invasive hysterectomies (MIS) were included. Clinical and surgical variables were analyzed and time to recurrence was compared between surgical groups. RESULTS: We identified 494 patients, of which 363 had MIS hysterectomies, 92.5% had endometrioid histology, 45.7% were stage IA and 48.0% stage IB. Open hysterectomy patients had higher BMIs (p = 0.007), lower rates of lymph node sampling (p < 0.001) and lymphovascular space invasion (LVSI) (p = 0.036), however in patients who recurred, no differences were noted between groups. Overall, 65 patients (13.2%) recurred, 14 in the open group (10.7%) and 51 in the MIS group (14.0%) (p = 0.58), while vaginal recurrences were noted in 4.6% and 6.1% respectively. When compared to the open group, the MIS group had a significantly shorter time to any recurrence (p = 0.022), to pelvic (p = 0.05) and locoregional recurrence (p = 0.021) and to death from any cause (p = 0.039). After adjusting for age, BMI, grade, LVSI and surgery date, the MIS group had a higher risk of any recurrence (HR 2.29 (1.07-4.92), p = 0.034) and locoregional recurrence (HR 4.18 (1.44-12.1), p = 0.008). CONCLUSIONS: Patients with HIR-EC treated with VBT after MIS hysterectomy have a shorter time to recurrence and higher risk of recurrence when compared to open hysterectomy patients. Further studies into the safety of MIS in high-intermediate risk patients are required.

UV irradiation induces apoptosis in the human endometrial stromal cell line (ThESC).

PURPOSE: The treatment options of endometrial hyperplasia consist of surgical, interventional and medical therapies including apoptosis-inducing agents. The purpose of the study was to evaluate the effects of ultraviolet (UV) radiation on the viability and the type of cell death on the human endometrial stromal cells (ThESC) line. METHODS: We investigated the effect of UV exposure on human endometrial stromal cell line (ThESC) on cell viability using MTT assay as well as changes in cell morphology using phase microscopy and acridine orange (AO)/ethidium bromide (EB) cell staining. RESULTS: UV treatment significantly decreased the percentage of the viable ThESC cells compared to the viability of untreated control cells using MTT assay (p<0.05). In addition, UV treatment of ThESC cells for 60 and 90 min induced high level of cell morphology disruption, followed with loss of both the cell shape and the presence of defragmented debris and stained with intense red color. CONCLUSIONS: The obtained results suggest the potential role of UV light application as additional treatment option of benign endometrium hyperplasia alone or in combination with other treatment modalities.

Laser irradiation pretreatment improves endometrial preparation of frozen-thawed embryo transfer in recurrent implantation failure patients.

Recurrent implantation failure (RIF) remains a clinical dilemma. Helium-Neon (He-Ne) laser irradiation has recently become more popular under certain clinical conditions. Given the unique therapeutic effects, we were interested in determining whether pretreatment with He-Ne laser irradiation prior to frozen-thawed embryo transfer (FET) would improve the microcirculation and cause the release of growth factors and cytokines, thus improving endometrial receptivity and the clinical pregnancy rates. Patients chose for themselves whether to proceed with (n = 29) or without (n = 31) pretreatment with He-Ne laser irradiation prior to FET. The clinical pregnancy rate (37.9%) and implantation rate (20.3%) were higher in the laser-treatment group than in the control group (35.5% and 15.9%, respectively, p = .844 and .518, respectively). The live birth rate was higher in the laser-treatment group (27.6% vs. 25.8%, respectively, p = .876) and the miscarriage rate was lower in the laser-treatment group (18.2% and 27.3%, respectively, p = .611). No side effects or complications from laser irradiation were encountered in patients who received the laser treatment. We concluded that pretreatment with He-Ne laser prior to FET may be an alternative choice for RIF-affected women; however, additional well-designed prospective studies are necessary to determine the precise clinical value of this treatment.

Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells.

Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro decidualization using primary human eSCs. Exposure to SM for 36 h decreased the proliferation and migration of eSCs significantly, without inducing cell death and changes in cell cycle progression. The phosphorylation of Akt decreased under SM conditions in human eSCs, accompanied by a simultaneous decrease in the level of matrix metalloproteinase (MMP)-2 and FOXO3a. Treatment with Akti, an Akt inhibitor, decreased MMP-2 expression, but not FOXO3a expression. The decreased level of FOXO3a under SM conditions impeded autophagic flux by reducing the levels of autophagy-related genes. In addition, pre-exposure of eSCs to SM significantly inhibited 8-Br-cAMP induced decidualization, whereas restoration of the growth status under SM conditions by removing 8-Br-cAMP remained unchanged. Treatment of human eSCs with SC-79, an Akt activator, restored the reduced migration of eSCs and decidualization under SM conditions. In conclusion, exposure to SM inhibited decidualization in eSCs by decreasing proliferation and migration through Akt/MMP and FOXO3a/autophagic flux.

Adjuvant chemoradiotherapy vs. radiotherapy alone in early-stage high-risk endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: The benefits of adjuvant chemoradiotherapy (CRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) stages I-II high-risk endometrial cancer remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of CRT over radiotherapy (RT) in patients with early-stage high-risk endometrial cancer. PATIENTS AND METHODS: We searched MEDLINE (from 1946 to May 2018), EMBASE (from 1966 to May 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for endometrial cancer comparing CRT to RT alone. The outcomes were overall survival (OS), failure-free survival (FFS), local recurrence rates (LRR) and the distant metastasis rate (DMR). RESULTS: Three eligible studies with 1120 participants were included in the meta-analysis. All studies were published from 1990 to 2018. The OS rates were 82.5% for the patients in the CRT group and 84.4% for patients in the RT group. The included three RCTs showed no significant difference of OS between the CRT and RT groups (odd ratio 0.98, 95% CI 0.93 to 1.02, p=0.35) with no heterogeneity (I2=0%, p=0.47). Two studies reported 382 FFS events in 469 patients with CRT treatment (81.4%) and 376 events of the 470 patients with RT treatment (80.0%). Overall, CRT group didn't provide any benefit over RT alone (1.02, 0.95 to 1.08, p=0.62; I2 = 0%, p=0.55) in FFS. 39 patients in CRT group (10.2%) vs. 16 patients in RT group (4.3%) were diagnosed with local recurrence. LRR was significantly more common in patients receiving adjuvant chemoradiotherapy compared with adjuvant radiotherapy (2.29, 1.31 to 3.98, p=0.004; I²=0%, p=0.33). The distant metastasis occurred in 20 patients (5.2%) treated with CRT and 26 patients (7.0%) treated with RT. The effect of reducing DMR was equivocal between the CRT group and the RT group, with an OR of 0.74 (0.43-1.27, p=0.28; I²=0%, p=0.87). CONCLUSIONS: This study demonstrates that adjuvant chemoradiotherapy has no advantage over radiotherapy alone for overall survival and failure-free survival in high-risk patients with FIGO stages I-II endometrial cancer. In addition, CRT is associated with a high risk of local recurrences.

Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial.

OBJECTIVE: The Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-4a trial is a randomized trial for women with high-intermediate risk endometrial cancer (EC), comparing individualized adjuvant treatment based on a molecular-integrated risk profile to standard adjuvant treatment; vaginal brachytherapy. To evaluate patient acceptability and pathology logistics of determining the risk profile, a pilot phase was included in the study. METHODS: PORTEC-4a is ongoing and the first 50 patients enrolled were included in the pilot phase. Primary endpoints of the pilot phase were patient acceptance, evaluated by analyzing the screening logs of the participating centers, and logistical feasibility of determination of the risk profile within 2 weeks, evaluated by analyzing the pathology database. RESULTS: In the first year, 145 eligible women were informed about the trial at 13 centers, of whom 50 (35%) provided informed consent. Patient accrual ranged from 0 to 57% per center. Most common reasons for not participating were: not willing to participate in any trial (43.2%) and not willing to risk receiving no adjuvant treatment (32.6%). Analysis of the pathology database showed an average time between randomization and determination of the molecular-integrated risk profile of 10.2 days (1-23 days). In 5 of the 32 patients (15.6%), pathology review took >2 weeks. CONCLUSIONS: The PORTEC-4a trial design was proven feasible with a satisfactory patient acceptance rate and an optimized workflow of the determination of the molecular-integrated risk profile. PORTEC-4a is the first randomized trial to investigate use of a molecular-integrated risk profile to determine adjuvant treatment in EC.

Extremely low-frequency electromagnetic field (EMF) generates alterations in the synthesis and secretion of oestradiol-17ß (E2) in uterine tissues: An in vitro study.

An electromagnetic field (EMF) of extremely low frequency may affect physiological processes in mammals. The aim of the present study was to determine the effect of an EMF on the synthesis and secretion of oestradiol-17ß (E2) in the porcine uterus. Endometrial and myometrial slices were harvested on days 12-13 of the oestrous cycle and exposed in vitro to an EMF (50 and 120 Hz, 8 mT) for 2 and 4 h in the presence or absence of progesterone (P4). Subsequently, the incubation media were used to determine the concentration of E2 with RIA. Tissues fragments were used to study the expression of CYP19A3 mRNA using Real-Time PCR and the abundance of P450 aromatase using Western Blotting. The 50-Hz EMF increased E2 release from the endometrium and the myometrium at both time points of in vitro incubation. A 120-Hz EMF decreased the endometrial secretion of E2 after 2 h of incubation and did not affect E2 secretion after 4 h. In the myometrium, the 120-Hz EMF increased E2 secretion after 4 h of incubation. In P4-treated uterine fragments, no significant EMF exposition-related changes were observed. Only myometrial fragments incubated in the presence of P4 at 120-Hz EMF (4 h) released higher amounts of E2 due to EMF treatment. The 50-Hz EMF exposure did not change the CYP19A3 mRNA expression in endometrial fragments incubated in the presence or absence of P4. In myometrial fragments, the highest CYP19A3 mRNA expression was observed in fragments not exposed to the 50-Hz EMF and P4-treated tissues compared to that in fragments exposed to 50 Hz EMF and incubated with or without P4 and control (no EMF and no P4) fragments. The EMF at 120 Hz decreased basal endometrial CYP19A3 mRNA expression and did not change the expression in the P4-treated endometrium. In the myometrium, the EMF at 120 Hz increased CYP19A3 mRNA expression in slices incubated without P4 and had no effect in the presence of P4. The EMF exposure (50 and 120 Hz) did not affect P450 aromatase abundance in either the endometrium or the myometrium. In conclusion, the EMF induces changes in the synthesis and release of E2 in uterine tissues harvested during days 12-13 of the oestrous cycle. These changes are related to the EMF frequency used, the time of the exposition and the presence of P4. We suspect that this observed phenomenon might lead to changes in the intrauterine milieu of oestrogen, which is crucial for the proper activity of uterine tissues during the mid-luteal phase of the oestrous cycle.

[The application of low-frequency ultrasound for the comprehensive treatment and rehabilitation of the patients presenting with chronic endometritis]. / Primenenie nizkochastotnogo ul'trazvuka v kompleksnoi terapii i reabilitatsii patsientok s khronicheskim éndometritom.

The incidence of chronic endometritis remains rather high despite considerable progress in reproductive medicine including the advent of the new methods for assisted reproduction; the pregnancy rate after the treatment of this condition is still unacceptably low. It implies the necessity of the careful preparation of endometrium for the implantation of the embryo especially in women with a history of unsuccessful outcomes of the IVF treatment. It calls for the development of the efficient therapeutic modalities for the management of chronic endometritis and restoration of the normal reproductive function; their introduction into the therapeutic algorithm remains equally relevant. The characteristic features of chronic endometritis include blood circulatory disorders in the vessels of the uterus and in the pelvic vascular basin, changes of local immunity in the endometrium concomitant with the activation of cellular and humoral responses of inflammation in the form of enhanced leukocyte infiltration and increased production of cytokines. The long duration of such a process results in the development of fibrosis that, in its turn, leads to chronic tissue hypoxia, potentiation of inflammation, and disruption of decidualization that hampers successful implantation. The article shows the possibility of using low-intensity ultrasound for the treatment and rehabilitation of the patients presenting with chronic endometritis. The data concerning the primary biophysical processes developing in the tissues under the influence of ultrasound are discussed. The therapeutic effects and their underlying mechanisms and described. The physiotherapeutic treatment considerably improved vascular hemodynamics in the pelvic basin and produced trophotropic, defibrosing, and anti-inflammatory effects. The clinical data giving evidence of the high effectiveness of the application of intrauterine ultrasound cavitation provide a basis for the recommendation to include this physical factor in the existing algorithms for the pre-gravid preparation of the women presenting with disorders of the reproductive function and chronic endometritis.

The Protective Effect of N-Acetylcysteine on Ionizing Radiation Induced Ovarian Failure and Loss of Ovarian Reserve in Female Mouse.

Ionizing radiation may cause irreversible ovarian failure, which, therefore, calls for an effective radioprotective reagent. The aim of the present study was to evaluate the potential radioprotective effect of N-acetylcysteine (NAC) on ionizing radiation induced ovarian failure and loss of ovarian reserve in mice. Kun-Ming mice were either exposed to X-irradiation (4 Gy), once, and/or treated with NAC (300 mg/kg), once daily for 7 days before X-irradiation. We examined the serum circulating hormone levels and the development of ovarian follicles as well as apoptosis, cell proliferation, and oxidative stress 24 hours after X-irradiation. In addition, morphological observations on the endometrial luminal epithelium and the fertility assessment were performed. We found that NAC successfully restored the ovarian and uterine function, enhanced the embryo implantation, improved the follicle development, and altered the abnormal hormone levels through reducing the oxidative stress and apoptosis level in granulosa cells while promoting the proliferation of granulosa cells. In conclusion, the radioprotective effect of NAC on mice ovary from X-irradiation was assessed, and our results suggested that NAC can be a potential radioprotector which is capable of preventing the ovarian failure occurrence and restoring the ovarian reserve.

[New challenges to the treatment of cervical intraepithelial neoplasia].

Due to the progress of intracavitary afterloading technology and dosage of brachytherapy, a similar dose distribution as that of cervical conization can be achieved and can be applied to the treatment of cervical intraepithelial neoplasia (CIN), it is called "afterloading conization" . Being adjusted the radioactive source movement and weight, low exposure doses to the ovary, endometrium and vagina can be assured. So a high quality of life after treatment could be maintained and overcomes the shortcomings of cervical conization and hysterectomy, such as anesthesia, bleeding, over or insufficient treatment, early ovarian ageing and operative complications.

Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells.

PURPOSE: Lipocalin 2 (LCN2) is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear. METHODS: The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV) irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively. RESULTS: LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05). Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt) was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing. CONCLUSIONS: These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.

Acute effects of pelvic irradiation on the adult uterus revealed by dynamic contrast-enhanced MRI.

OBJECTIVE: Pelvic radiation therapy (RT) can influence fertility in female rectal cancer survivors. Data regarding its effects on the adult uterus are scant. This study aims to evaluate the uterus before and after RT, using dynamic contrast-enhanced MRI. METHODS: Eligible patients (n=10) received RT for rectal cancer, had an intact uterus and underwent dynamic contrast-enhanced MRI before and after RT. Seven patients were pre-menopausal. RESULTS: Patients received pelvic RT (median, 50.2 Gy) with concurrent 5-fluorouracil. Five patients were treated with intensity modulated RT (IMRT) and five with a three-field technique. The median D95 of the uterus was 30 Gy; D05 was 48 Gy; and V95 was 97%. The median cervical D95 was 45 Gy; D05, 50 Gy; and V95, 100%. Cervical dose was higher with IMRT than with three-field plans (p≤0.038). On T2 MRI, the junctional zone was visible in nine patients before and in one after RT (p=0.001). Median cervical length (2.3 vs 3.0 cm) and endometrial thickness (2.6 vs 5.9 mm) were reduced after RT (p≤0.008). In pre-menopausal patients, the volume transfer constant, K(trans), (0.069 vs 0.195, p=0.006) and the extracellular extravascular volume fraction, V(e), (0.217 vs 0.520, p=0.053) decreased. CONCLUSION: Pelvic RT significantly affected uterine anatomy and perfusion. Cervical dose was higher with IMRT than three-field plans, but no attempt was made to constrain the dose. ADVANCES IN KNOWLEDGE: Pelvic RT significantly affects the adult uterus. These findings are crucial to understand the potential consequences of RT on fertility, and they lay the groundwork for further prospective studies.

Adjuvant sequential chemoradiation therapy in high-risk endometrial cancer: results of a prospective, multicenter phase-II study of the NOGGO (North-Eastern German Society of Gynaecological Oncology).

PURPOSE: The management of high-risk endometrial cancer (HREC) remains controversial. We conducted a prospective multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy (CT) with sequential radiotherapy (RT) in patients with HREC. METHODS: Patients with HREC from 8 institutions in Germany were enrolled. After surgery, patients received four cycles of paclitaxel 175 mg/m² (P) and carboplatin AUC5 (C) (d1, q21d) and subsequent external pelvic radiation therapy (1.8 Gy/d, d1-5) at a total dose of 45 Gy with vaginal brachytherapy (3 × 5 Gy). Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Primary endpoints were tolerability, toxicity and QoL. Progression-free survival (PFS) was defined as secondary endpoint. RESULTS: Thirty-five patients were enrolled from 2004 through 2008. Median follow-up was 24 months (range 3-24 months). All patients received 4 cycles of P and C and completed RT. Overall, grade 3/4 haematological toxicity was 25.6 %. Three cycles were delayed because of leukopenia. Grade 3/4 non-haematologic toxicities were rare (≤3 %). No overall change in QoL occurred during treatment. Two-year median PFS and OS rates were both 75.8 %. CONCLUSIONS: Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC. Subsequent phase-III trials are warranted.

Multidisciplinary treatment of early stage endometrial cancer.

Endometrial cancer is a highly curable malignancy when it presents as uterine-confined disease, but the prognosis for metastatic or recurrent endometrial cancer is poor. For those patients which are diagnosed at an early stage, surgery alone may be adequate for cure and clinical outcome is often favorable, with approximately 80 % of cases surviving at 5 years. However, after primary diagnosis and treatment, roughly 20-30% of patients are expected to recur within the following 5 years. Adjuvant treatment for endometrial cancer is not yet clearly defined. FIGO Stage I-III endometrial cancer patients, usually undergo surgery and some of them are offered adjuvant treatment based on risk assessment. Grade, age, stage are considered all independent risk factors for recurrence. Radiotherapy (RT) has been considered the adjuvant treatment of choice for decades, being able to reduce local recurrence rate and improving progression free survival, but without any impact on overall survival. In the last two decades, a shift toward the use of systemic chemotherapy (CT) in addition or instead of radiation has occurred, although few prospective studies have been performed in this field.

Gamma-ray energy absorption and exposure buildup factor studies in some human tissues with endometriosis.

Human tissues with endometriosis have been analyzed in terms of energy absorption (EABF) and exposure (EBF) buildup factors using the five-parameter geometric progression (G-P) fitting formula in the energy region 0.015-15 MeV up to a penetration depth of 40 mfp (mean free path). Chemical compositions of the tissue samples were determined using a wavelength dispersive X-ray fluorescence spectrometer (WDXRFS). Possible conclusions were drawn due to significant variations in EABF and EBF for the selected tissues when photon energy, penetration depth and chemical composition changed. Buildup factors so obtained may be of use when the method of choice for treatment of endometriosis is radiotherapy.

Hysteroscopic appearance of endometrial cavity after microwave endometrial ablation.

STUDY OBJECTIVE: To assess the appearance of the endometrial cavity after microwave endometrial ablation. DESIGN: Prospective observational study. SETTING: GuangDong Women's and Children's Hospital, GuangDong, China. PATIENTS: A total of 349 patients who underwent microwave endometrial ablation from January 2000 through August 2008 were followed up for 1 month to 8 years. At follow-up in 2007 and 2008, patients were advised of this clinical study and were randomly selected for participation if they agreed to undergo outpatient hysteroscopy to assess the uterine cavity during follow-up visits. Fifty three patients (median [range] age, 43.1 [33-53] years) were recruited into the study at the time of endometrial ablation. INTERVENTION: Outpatient hysteroscopy. MAIN RESULTS: Within the first 3 months after ablation, outpatient hysteroscopy revealed varying amounts of necrotic tissue from the endometrium and superficial myometrium of the uterus. Six months postablation, a granulomatous reaction and fibrosis were present. A fibrotic cavity was also evident, and menstrual flow was reduced or had ceased. One year after ablation, hysteroscopy demonstrated a fibrotic cavity with myofibrous scars. Most patients developed amenorrhea at this time. Two years or more postablation, a second hysteroscopy demonstrated various types of intrauterine adhesions in 28 of the 53 women (52.8%). A cervical adhesion was observed in 1 patient (1.9%), focal adhesions in the fundal area in 12 (22.6%), a narrowed and scarred uterine cavity with bilateral stenotic tubal ostia in 11 (20.7%), and complete obliteration of the cavity in 4 (7.5%). Of these 28 women, 22 had amenorrhea, 3 had vaginal spotting during menstruation, and 2 had hypomenorrhea. Of those without intrauterine adhesions, only 5 had amenorrhea, 10 had vaginal spotting, and 8 had hypomenorrhea. CONCLUSION: The hysteroscopic appearance of the uterine cavity after microwave endometrial ablation varies considerably. In this study, the menstrual outcome was correlated with postablation uterine cavity appearance.

Effects of extremely low-frequency electromagnetic field on fertility and heights of epithelial cells in pre-implantation stage endometrium and fallopian tube in mice.

OBJECTIVE: To investigate the effects of extremely low-frequency electromagnetic field (ELF-EMF) on fertility and heights of epithelial cells in pre-implantation stage endometrium and fallopian tube in mice. METHODS: Eighty female NMRI mice were randomly divided into 2 groups: control group was not exposed to EMF and experimental group was exposed to 4-hour EMF per day, 6 days a week for 2 weeks to 50 Hz, 0.5 mT EMF. Female mice in two groups were superovulated and mated with male mice over night. At the time of implantation, the blastocysts were obtained from the presumed pregnant mice with vaginal plug by flushing the uterus horns. The samples of uterus horns and fallopian tubes in two groups were taken and were processed for light microscopic studies. RESULTS: The analysis of mean number of the flushed blastocysts in the EMF group showed significant decrease as compared with the control group (P<0.03). Light microscopic study showed that the height of fallopian tube epithelial cells was significantly increased in the EMF group as compared with the control group (P<0.001). However the height of endometrial epithelial cells in the EMF group showed insignificant increase as compared with the control group. CONCLUSION: The results indicate that ELF-EMF has detrimental effect on female reproductive system in mice by decreasing the number of flushed blastocysts and increasing the height of fallopian tube epithelial cells.