A Case Report of Occult Breast Cancer Detected by Diagnostic Laparoscopy for Suspected Ovarian Cancer.

Diagnostic laparoscopy is useful in the management of gynecological cancers; however, it can occasionally result in the detection of other malignancies. Occult breast cancer (OBC) is metastatic breast cancer without a recognized primary breast lesion. We report a rare case of OBC that was detected laparoscopically. A 64-year-old female presented to our hospital with back pain. Magnetic resonance imaging (MRI) revealed a 50 mm multicystic tumor with an internal nodule in the right ovary. Positron emission tomography/computed tomography showed abnormal accumulation in multiple lymph nodes, moderate accumulation in the ovarian tumor nodule, and no accumulation in the breasts. Ovarian cancer was suspected, and a diagnostic laparoscopy was performed. Laparoscopically, a cystic tumor in the right ovary and 10 mm nodule in the right round ligament were observed and partially resected. Immunohistopathologically, the nodules of the round ligament exhibited features consistent with those of breast cancer, but the ovarian tumor was a seromucinous borderline tumor. MRI revealed no breast lesions. Therefore, the malignancy was diagnosed as an OBC.

Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium.

Menstrual blood, containing high iron levels, can undergo retrograde transport into the abdominal cavity. Excess iron causes oxidative stress and inflammation. Iron metabolism is regulated by hepcidin, and serum hepcidin levels are increased in patients with endometriosis; however, the functions of hepcidin in normal endometrium remain unclear. We therefore aimed to examine hepcidin concentrations in patients with endometriosis and to determine if iron accumulation and hepcidin increased the production of reactive oxygen species (ROS) and inflammation in normal endometrial cells. We determined hepcidin levels in peritoneal fluid and menstrual blood from patients with and without endometriosis (25/16 and 15/15 patients, respectively). We also examined the effects of hepcidin on ferroportin expression, iron accumulation, and ROS generation in normal endometrial stromal cells (NESCs) from 20 women who underwent surgery for uterine leiomyoma, using immunohistochemistry and immunofluorescence analyses and analyzed its effect on the expression of inflammatory cytokines by real-time polymerase chain reaction. There was no significant difference in iron concentrations in menstrual blood or peritoneal fluid between women with and without endometriosis; however, women with endometriosis had significantly higher hepcidin levels in menstrual blood. Hepcidin reduced the expression of ferroportin in NESCs and promoted the accumulation of ferrous iron. Hepcidin plus ferrous iron increased the production of ROS and inflammatory cytokines compared with ferrous iron alone. These results indicate that women with endometriosis have high hepcidin levels in menstrual blood, leading to increased iron production, oxidative stress, and inflammation, which may, in turn, promote the development of endometriosis.

Postoperative Pregnancy Outcomes Following Laparoscopic Surgical Management in Women with Stage III/IV Endometriosis: A Single-Center Follow-Up Study.

Objectives: The effects of laparoscopic surgical management in women with stage III/IV endometriosis remain controversial. The standard extent of resection for stage III/IV endometriosis with deep endometriosis to treat endometriosis-associated infertility is debatable. This study aimed to assess the postoperative pregnancy outcomes following a routine surgical intervention for stage III/IV endometriosis patients. Materials and Methods: Patients with stage III/IV endometriosis who underwent conservative laparoscopic surgery at our hospital between January 2010 and December 2018 were retrospectively analyzed. Statistical analyses were performed to determine the correlations between endometriosis features and postoperative pregnancy outcomes. Results: Of 256 patients enrolled, 94 wished to conceive. Exclusion criteria: ≥40 years, adenomyosis, partners with infertility issues. Finally, 71 women were included. The overall postoperative pregnancy rate was 76.1% (n = 54): 49 and five from non-assisted reproductive technology (ART) and ART, respectively. The postoperative pregnancy rate in patients diagnosed with infertility presurgery (40/71) was 70.0% (n = 28): 24 (non-ART) and four (ART). The endometriosis fertility index (EFI) score was higher in the pregnant than in the nonpregnant group (P = 0.03). The EFI score and surgical score of EFI were higher in the non-ART than in the ART group (P = 0.04; P = 0.02); in the infertile group, they were higher in the pregnant than in the nonpregnant group (P = 0.018; P = 0.027). Conclusion: Our postoperative pregnancy rate after conservative laparoscopic surgery for patients with stage III/IV endometriosis compared favorably with previous reports. EFI was a significant predictor of postoperative pregnancy. Our surgical approach to maintain a high surgical score of EFI might help treat endometriosis-associated infertility.

Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis.

Although nutrient status plays an important role in cell metabolism, its significance in endometriosis is obscure. Herein, we investigated the effects of a low-nutrient microenvironment on endometriosis. Stromal cells (SCs) from ovarian endometrioma (OESCs) or normal endometrium without endometriosis (NESCs) were isolated and cultured. A low-nutrient microenvironment was replicated by replacing the culture medium with Hank's balanced salt solution. OESC and NESC proliferation under the low-nutrient condition was measured. The expression of exacerbating factors in endometriosis under the low-nutrient condition was examined at the mRNA and protein levels. OESCs showed higher proliferation than NESCs under the low-nutrient condition. In OESCs, the low-nutrient condition upregulated the mRNA expression of vascular endothelial growth factor (VEGF), interleukin-6 and -8, aromatase, Bcl-2, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and downregulated that of BAX and induced transcription of PI.3, PII, and exon II. Western blotting revealed elevated VEGF and PGC-1α expression under the low-nutrient condition in OESCs. These changes coincided with the elevated expression of PGC-1α, which was reduced at the mRNA level upon nutrient status rescue. Endometriosis is exacerbated by altered angiogenesis, inflammation, anti-apoptosis, and local estrogen production while trying to survive under a low-nutrient microenvironment; it may be attributed to PGC-1α-mediated metabolic mechanisms.

Dienogest does not augment the gene expression of adhesion molecules, MCP-1, and monocyte adherence in human endothelial cells.

OBJECTIVE: Medroxyprogesterone acetate (MPA) may increase the risk of atherosclerosis during hormone replacement therapy (HRT); therefore, the effect of progestogens other than MPA on atherosclerotic lesions requires evaluation. Adhesion of monocytes to vascular endothelial cells is an important early step in atherosclerosis progression. MCP-1 is a key chemokine that promotes monocyte migration and adhesion to vascular endothelial cells. In this study, we investigated the effects of dienogest (DNG), an alternative progestogen, on monocyte adhesion and cytokine expression in human umbilical vein endothelial cells (HUVECs). STUDY DESIGN: HUVECs were treated with DNG, natural progesterone, or MPA, followed by interleukin (IL)-1ß stimulation. The mRNA expression of adhesion molecules (E-selectin and ICAM-1) and cytokines (MCP-1 and IL-6) was examined using real-time PCR. A flow chamber system was used to examine the effect of DNG on the adhesion of U937 monocytic cells to monolayer HUVECs. RESULTS: Unlike MPA, DNG did not alter the mRNA expression of E-selectin, ICAM-1, MCP-1, and IL-6 in HUVECs. Moreover, it did not increase the number of monocytes adhering to HUVECs in the flow chamber system. However, MPA treatment significantly enhanced monocyte adhesion to HUVECs (p < 0.05). CONCLUSIONS: DNG had no effect on the mRNA expression of adhesion molecules and cytokines in HUVECs, as well as the monocyte adhesion to HUVECs, suggesting that DNG can be explored as an alternative to MPA for HRT.

Changes in the proportion of regulatory T cell subpopulations during menstrual cycle and early pregnancy.

PROBLEM: Regulatory T cells (Tregs) play important roles in diseases occurring in women of reproductive age and pregnancy. Tregs are functionally heterogeneous and can be divided into activated Tregs (aTregs), resting Tregs (rTregs), and non-suppressive Tregs (non-Tregs). The purpose of this study is to investigate the change of Treg subpopulations during the menstrual cycle and early pregnancy. METHOD OF STUDY: Two groups of women were enrolled: healthy women aged 20 to 39 years with normal menstrual cycles and patients scheduled to undergo frozen-thawed blastocyst transfer (FT-BT) (subfertile women). Peripheral blood samples were collected at day 5 of the onset of menstruation (follicular phase), 0-2 days after luteinizing hormone (LH) surge (periovulatory phase), and 7-11 days after LH surge (luteal phase) from 20 healthy women. From 23 subfertile women, samples were collected at day 5 (the day of BT) and day 14 (the day of pregnancy testing) of progestogen administration during FT-BT cycle and 9 weeks of gestation if the patient got pregnant. The proportion of total Treg and its subpopulations among CD4+ T cells was analyzed. RESULTS: TTreg and aTreg proportion expanded during periovulatory phase (p < .01) and after pregnancy (p < .05 for tTreg and p < .01 for aTreg). rTreg proportion was significantly high during periovulatory phase (p < .01) and during luteal phase (p < .01). Non-Tregs showed no significant change. CONCLUSIONS: RTregs and aTregs, especially in luteal phase and after getting pregnant, showed significant changes and may play important roles in women of reproductive age.

Robot-assisted laparoscopic hysterectomy for early-stage endometrial cancer with massive uterine leiomyomas: A case report.

INTRODUCTION AND IMPORTANCE: Compared to conventional laparoscopic surgery, robot-assisted surgery enables precise operation, with the aid of high-resolution 3D images and articulated forceps, even in cases where the uterus is very large. CASE PRESENTATION: A 48-year-old woman with severe obesity was referred to our hospital with atypical genital bleeding for half a year. She was diagnosed with multiple uterine leiomyomas and early endometrial cancer with presumed advanced stage classification (stage IA). Robot-assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node biopsy were performed. Due to the difficulty of removing the uterus transvaginally, the umbilical incision was extended by 7 cm, which allowed the uterine tissue removal without shredding or leakage into the pelvic cavity. The patient was discharged 5 days postoperatively, with no postoperative complications. CLINICAL DISCUSSION: Robot-assisted surgery has often been used for the management of early-stage endometrial cancer. Robot-assisted laparoscopic hysterectomy has significantly fewer intraoperative and postoperative complications than laparoscopic and abdominal hysterectomy. CONCLUSION: Improving this surgical procedure allows for safe and easy robot-assisted uterine malignant tumor removal even in cases where the patient presents with severe obesity and huge uterine leiomyomas.

Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis.

CONTEXT: Progesterone resistance including progesterone receptor (PR) deficiency contributes to the pathophysiology of endometriosis; however, whether the PR expression levels in ovarian endometrioma (OE) correlate with the postoperative recurrence of endometriosis remains unclear. OBJECTIVE: This study aimed to investigate the association between PR expression levels in OE and the recurrence of endometriosis. METHODS: OE specimens were obtained from 132 patients who underwent conservative surgery for endometriosis. The PR expression levels were evaluated using the H score after immunohistochemical staining. RESULTS: Of the 132 patients, 36 (27.3%) experienced recurrence and 96 (72.7%) did not. No differences were observed in the patient characteristics between the recurrence and nonrecurrence groups except for follow-up period. PR immunoreactivity in the epithelial cells (ECs) was statistically significantly lower in the recurrent group than in the nonrecurrent group (P < .01); however, this change was not observed in the stromal cells. Moreover, multivariable logistic regression analysis revealed that the H score of PR in ECs was an independent factor and was statistically significantly associated with the recurrence of endometriosis (P = .01). Furthermore, we divided the patients into PR-negative or PR-positive groups. The cumulative recurrence rate in the negative PR group was statistically significantly higher than that in the positive PR group (P = .046). CONCLUSION: Low PR expression levels in OE-ECs may predict the recurrence of endometriosis. The PR status in OE-ECs is associated with the pathophysiology of the recurrence of endometriosis, and optimized postoperative management for endometriosis may be provided by referring to the PR status.

Primary Ovarian Leiomyoma Associated with Multiple Uterine Leiomyomas.

Ovarian leiomyomas are very rare. We report the case of a primary ovarian leiomyoma accompanied by multiple uterine leiomyomas. A 50-year-old woman was referred to our department for heavy menstruation, and a hot spot in the uterine lumen was observed on positron emission tomography-computed tomography (PET-CT). Cervical and endometrial cytology and tumor marker tests were negative. Pelvic magnetic resonance imaging revealed an endometrial polyp and submucosal leiomyoma in the uterine lumen and a 5-cm right ovarian tumor. Laparoscopic total hysterectomy, right salpingo-oophorectomy, and left salpingectomy were performed for radical treatment. Histopathology showed that ovarian tumors contained interlacing bundles of fusiform cells encircled by normal ovarian tissue. Immunohistochemical staining showed strong and diffuse positive staining for α-smooth muscle actin. We diagnosed the tumor as a primary ovarian leiomyoma because the leiomyoma was localized in the ovary and was larger than the size of uterine leiomyomas. No metastatic lesion was found on PET-CT. There was no tumor recurrence at the 6-month follow-up.

Severe coronavirus disease pneumonia in a pregnant woman at 25 weeks' gestation: A case report.

There are numerous reports on the effects of the coronavirus disease on mothers and fetuses during pregnancy. It is currently unknown whether pregnancy is associated with a high risk of severe coronavirus disease. We report a pregnant patient with coronavirus disease who underwent a cesarean section. A pregnant 39-year-old Japanese woman was diagnosed with coronavirus disease at 25 weeks of gestation. Her breathing condition worsened daily, and she required oxygen administration. On day 6 of her 26th week of gestation, she developed severe pneumonia and required tracheal intubation and artificial ventilation, and an emergency cesarean section was performed under general anesthesia. It is necessary to investigate the risk of increased coronavirus disease severity during pregnancy, the effects of coronavirus disease on perinatal prognosis, and the management of pregnancy with coronavirus disease.

Interleukin-9 produced by helper T cells stimulates interleukin-8 expression in endometriosis.

PROBLEM: Inflammation and immune responses play crucial roles in the development of endometriosis. Although interleukin-9 (IL-9) has a pro-inflammatory function in chronic inflammatory diseases, its function in endometriosis remains unknown. Here, we aimed to investigate the significance of IL-9 and IL-9-producing lymphocytes in endometriosis. METHOD OF STUDY: Specimens were obtained from patients with and without endometriosis. Peritoneal fluid (PF), peripheral blood (PB), and ovarian endometrioma (OE) tissues were analyzed for the proportion of CD4+ IL-9+ lymphocytes and IL-9 concentration using flow cytometry and enzyme-linked immunosorbent assay. OE, endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for IL-9 receptor (IL-9R) expression using immunohistochemical staining. IL-9-dependent changes in Interleukin-8 (IL-8) expression in endometrial stromal cells from OE (OESCs) were evaluated using real-time PCR. RESULTS: The proportion of CD4+ IL-9+ lymphocytes was higher in the PF, but not the PB, of patients with endometriosis than individuals without endometriosis (p < .05). However, IL-9 levels in the PF did not differ between those with and without endometriosis. We detected CD4+ IL-9+ lymphocytes in OE tissues and IL-9R in OE tissues and OESCs. In OESC culture, IL-9 significantly elevated IL-8 expression in a dose-dependent manner (p < .05), which was nullified by the addition of the anti-IL-9 receptor antibody. Furthermore, IL-9 additively stimulated IL-8 expression in the presence of TNF-α (p < .05). CONCLUSION: Our findings show that IL-9 produced by helper T cells induces IL-8 expression, suggesting that IL-9 plays an important role in the development of endometriosis by stimulating IL-8 expression.

Prenatal diagnosis of fetal skeletal dysplasia using 3-dimensional computed tomography: a prospective study.

BACKGROUND: Fetal skeletal dysplasia (FSD) comprises a complex group of systemic bone and cartilage disorders. Many FSD phenotypes have indistinct definitions, making definitive prenatal diagnosis difficult. The condition is typically diagnosed using sonography; however, three-dimensional computed tomography (3D-CT) also aids in making a prenatal diagnosis. This study aimed to examine the efficacy of 3D-CT in the prenatal diagnosis of FSD by comparing the diagnostic accuracy of fetal sonography and 3D-CT. METHODS: On suspicion of FSD based on ultrasound examination, we performed 3D-CT prenatally to obtain detailed skeletal information on FSD. To minimize exposure of the fetuses to radiation without compromising image quality, we used predetermined 3D-CT settings for volume acquisition. RESULTS: Nineteen fetuses were suspected of having skeletal dysplasia based on ultrasonography findings. Of these, 17 were diagnosed with FSD using 3D-CT. All 17 fetuses diagnosed with FSD prenatally were confirmed postnatally to have the condition. The postnatal diagnosis (campomelic dysplasia) differed from the prenatal diagnosis (osteogenesis imperfecta) in only one infant. Sixteen cases (94.1%) were diagnosed both prenatally and postnatally with FSD. Five infants had lethal skeletal dysplasia; one died in utero, and four died as neonates. We determined the appropriate delivery method for each infant based on the prenatal diagnosis. CONCLUSIONS: 3D-CT is a valuable tool for augmenting ultrasound examinations in the diagnosis of FSD. While improving the diagnostic tool of sonography is essential in cases of suspected FSD, 3D-CT imaging is indispensable for diagnosis and classification, enabling better planning for resuscitation of the infant after birth. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Center trial registration number is UMIN000034744 . Registered 1 October, 2018 - Retrospectively registered.

Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy.

OBJECTIVE: Chronic inflammation in endometriosis is associated with increased risk of future cardiovascular disease; however, no studies have investigated the cardiovascular risk of women who have undergone hormonal therapy for endometriosis. We investigated atherosclerosis-related biomarkers in women with and without endometriosis and the effects of dienogest (DNG) and oral contraceptive (OC) therapies. STUDY DESIGN: In this cross-sectional study, 109 women with endometriosis and 42 control women without endometriosis were enrolled. The endometriosis group was divided into the untreated (n = 34), DNG therapy (n = 33), and OC therapy (n = 42) groups. Lipid profile serum levels, inflammatory marker such as high-sensitivity C-reactive protein, oxidative stress markers such as oxidized low-density lipoprotein and diacron-reactive oxygen metabolites, and atherosclerosis indicators (cardio-ankle vascular index [CAVI] and ankle-brachial pressure index [ABI]) were measured. RESULTS: The median treatment duration was 28 months in the DNG group and 32.5 months in the OC group. Triglyceride levels were higher in the OC group than in the other three groups (P < 0.05). Regarding markers of inflammation and oxidative stress, log high-sensitivity C-reactive protein and diacron-reactive oxygen metabolites levels were higher in the untreated group than in the control group (P < 0.05), and these markers were further increased in the OC group (log high-sensitivity C-reactive protein: P < 0.05; diacron-reactive oxygen metabolites: P < 0.01), but not in the DNG group. There was no difference in the CAVI and ABI among all groups. Spearman correlation revealed a positive correlation between duration of OC therapy and CAVI (ρ = +0.49; P = 0.002), but no correlation between the duration of DNG therapy and CAVI (ρ = -0.04; P = 0.81). CONCLUSIONS: Inflammation and oxidative stress markers are increased in women with untreated endometriosis. Treatment with OC, but not with DNG, further increases these levels. There was a positive association between the duration of OC administration and atherosclerosis risk for women with endometriosis. Our results suggest that DNG could be administered to endometriosis without the increased atherosclerosis risk and short-term OC administration for endometriosis is not harmful, however, atherosclerosis risk should be strictly observed.

Protocol for a modified vaginal pipe for total laparoscopic hysterectomies: Experimental research.

BACKGROUND: The Vagi-Pipe® is a useful device for performing a total laparoscopic hysterectomy. The conventional model of the Vagi-Pipe® is unable to grasp the uterus during colpotomy for recovery of the resected uterus. However, the modified C-Type Vagi-Pipe® model has a shape that allows insertion into the vagina without removing the uterus manipulator. In this study, we will prospectively investigate the safety and efficacy of the C-Type Vagi-Pipe® in total laparoscopic hysterectomies. MATERIALS AND METHODS: In total, 25 female subjects aged between 20 and 60 years with uterine fibroids or adenomyosis will be included. Patients with complications regarded as unsuitable for this study by the investigators will be excluded. The C-Type Vagi-Pipe® will be used rather than the conventional Vagi-Pipe® when performing a total laparoscopic hysterectomy. The primary endpoint will be safety and the secondary endpoints will be operation time, bleeding volume, and presence of complications. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review boards. Written informed consent will be obtained from all patients before registration in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals.

Local estrogen formation and its regulation in endometriosis.

BACKGROUND: It has been well established that endometriosis is an estrogen-dependent disease. Although the exact pathogenesis of the disease is still unclear, it is known to be characterized by estrogen-dependent growth and maintenance of the ectopic endometrium and increased local estrogen production. METHODS: The authors reviewed studies on local estrogen production and estrogen activities mediated by estrogen receptors in endometriotic tissues. MAIN FINDINGS: Aberrant expression of several enzymes in local endometriotic lesions contributed to the production and metabolism of estrogens. Aromatase was one of the key therapeutic targets for the regulation of local estrogen formation. Our findings suggest that PGC-1a, a transcriptional coactivator-modulating steroid hormone, regulates aromatase expression and activity. Estrogen activities mediated by different types of estrogen receptors abnormally elevated in local tissues could also be involved in the development of endometriosis. The authors demonstrated that the isoflavone aglycone, a partial agonist of the estrogen receptor, suppressed the formation of endometriotic lesions. CONCLUSIONS: Local estrogen production and estrogen activity mediated by estrogen receptors are important potential therapeutic targets for endometriosis.

Peroxisome proliferator-activated receptor-γ coactivator 1α-mediated pathway as a possible therapeutic target in endometriosis.

STUDY QUESTION: Is a peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-mediated pathway involved in the development of endometriosis? SUMMARY ANSWER: PGC-1α plays critical roles in inflammation and cell proliferation of endometriotic tissues and may be involved in the development of endometriosis. WHAT IS KNOWN ALREADY: Expression levels of PGC-1α are higher in ovarian endometrioma (OE) than normal endometrium (NE). PGC-1α also stimulates aromatase activity and promotes local estrogen biosynthesis in OE. STUDY DESIGN, SIZE, DURATION: This is a case-controlled biological study using endometrial cells and tissues derived from 23 women with, and 10 women without, OE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ectopic endometriotic and eutopic endometrial stromal cells (SCs) were isolated and maintained in culture. PGC-1α was either overexpressed in the cells or knocked down using siRNA. The expression of PGC-1α and other factors during endometriosis was examined using real-time PCR and western blotting, cell proliferation was measured using Cell Counting Kit-8 (WST-8) assays and transcriptional activity was assessed using luciferase reporter assays. MAIN RESULTS AND THE ROLE OF CHANCE: PGC-1α overexpression promoted the proliferation of OESCs in a time-dependent manner (P < 0.01 versus control) but not NESCs. PGC-1α stimulated aromatase (P < 0.01 versus control) and interleukin (IL)-6/IL-8 mRNA expression levels (P < 0.05 versus control for each) and led to inhibitor kappa B phosphorylation protein expression and upregulation of the apoptosis inhibitors X-linked inhibitor of apoptosis protein and survivin at mRNA level (P < 0.05 versus control for each). HX531, a selective retinoid-X receptor-α (RXRα) antagonist, suppressed the PGC-1α-induced cell proliferation (P < 0.05 versus control), aromatase/IL-6/IL-8/survivin mRNA expression (P < 0.05 versus control for each) and transcription reporter activity of PGC-1α in a dose-dependent manner (P < 0.01 versus control). Moreover, HX531 downregulated PGC-1α-induced aromatase-promoter PI.3-II transcripts in OESCs, and PGC-1α knockdown reduced aromatase, IL-6/IL-8 and antiapoptotic factors mRNA expression (P < 0.05 versus control for each). Notably, the Histogram score, which was used for quantifying RXRα status, was markedly higher in OE than in NE tissue (P < 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Only OE tissues were included in this study, while peritoneal and deep infiltrating endometriotic tissues were not. Therefore, these findings might not be generalized to other types of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: In OESC, PGC-1α stimulated cell proliferation and was involved in local estrogen biosynthesis, inflammation and apoptosis, and these effects of PGC-1α were inhibited by HX531. The suppression of PGC-1α-induced proliferation by HX531 in OESCs but not NESCs suggests that the PGC-1α-RXRα axis could play critical roles in promoting endometriosis. This is the first report of a relationship between PGC-1α and inhibitor of apoptosis proteins in endometriosis. Based on these findings, the PGC-1α-mediated pathway could represent a potential target in molecular therapy of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The study is supported in part by Grants-in-Aid for Scientific Research (15 K10681 and 15 K10726) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan). The authors have no conflicts of interest to disclose.

Retroperitoneal fibrosis after chemo-radiotherapy for cervical cancer: A case report.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by proliferation of fibro-inflammatory tissue in the retroperitoneum. Multiple studies have reported on the idiopathic cases of the disease, but reports of RPF secondary to irradiation are very limited. Herein, we report the case of a 47-year-old woman who complained of lower abdominal pain 14 months after chemo-radiotherapy for cervical cancer. Computed tomography showed a soft-tissue mass spreading in the presacral space. Biopsy of the lesion revealed fibro-inflammatory tissue without malignancy. Retrospective imaging findings showed that the lesion was consistent with the irradiation field. We diagnosed the patient with RPF caused by radiotherapy. We started oral administration of prednisolone at a dose of 30 mg/day. After 3 months, scans showed a remarkable reduction in lesion size. Prednisolone was tapered to a maintenance dose of 5 mg/day, which is ongoing. The patient is doing well with no recurrence to date.

Equilin in conjugated equine estrogen increases monocyte-endothelial adhesion via NF-κB signaling.

The adhesion of monocytes to endothelial cells, which is mediated by adhesion molecules, plays a crucial role in the onset of atherosclerosis. Conjugated equine estrogen, which is widely used for estrogen-replacement therapy, contains both estrone sulfate and various nonhuman estrogens, including equilin. To investigate the association between various estrogen types and atherosclerosis risk, we examined their effect on adhesion-molecule expression in human umbilical vein endothelial cells (HUVECs). In estrogen-treated HUVECs, the mRNA and protein expression levels of adhesion molecules were quantified by real-time polymerase chain reaction and enzyme immunoassay. Additionally, a flow-chamber system was used to assess the effects of estrogens on the adherence of U937 monocytoid cells to HUVECs. Equilin, but not 17ß-estradiol (E2) or other types of estrogen, significantly increased the mRNA (P < 0.01) and protein (P < 0.05) expression of the adhesion molecules E-selectin and intercellular adhesion molecule-1 as compared with levels in controls. Equilin treatment increased the adherence of U937 monocytoid cells to HUVECs relative to the that in the control (P < 0.05), decreased estrogen receptor (ER)ß expression, and increased the expression of proteins involved in nuclear factor kappa-B (NF-κB) activation relative to levels in controls. Furthermore, the accumulation of NF-κB subunit p65 in HUVEC nuclei was promoted by equilin treatment. By contrast, E2 treatment neither increased the number of adhered monocytoid cells to HUVECs nor altered the expression of ERß or NF-κB-activating proteins. Our findings suggest that in terms of the adhesion of monocytes at the onset of atherosclerosis, E2 may be preferable for estrogen-replacement therapy. Further studies comparing equilin treatment with that of E2 are needed to investigate their differential impacts on atherosclerosis.

Massive prolapsed submucous fibroid treated with laparoscopic surgery: A case report.

Prolapsed uterine fibroids are pedunculated submucous fibroids that prolapse through the cervical canal. Herein, we describe the laparoscopic treatment of massive prolapsed submucous fibroids. A 47-year-old woman had experienced frequent urination and abnormal vaginal bleeding for 7 years. She presented with persistent lower abdominal pain. The uterine fundus was palpable at 3 cm above the umbilicus. Vaginal examination revealed a dark purple and easily bleeding mass in her vagina. Pelvic magnetic resonance imaging revealed a large mass prolapsing from the uterine endometrium, which occupied the cervical canal and vagina, without evidence of malignancy. Under a preoperative diagnosis of uterine fibroids with edematous degeneration, we performed laparoscopic uterine artery cutting, transvaginal removal of the fibroid by twisting, and total laparoscopic hysterectomy. Histopathological examination revealed leiomyoma with partial ischemia. Six days postoperatively, the patient was discharged without complications. This approach may be appropriate for the treatment of massive prolapsed submucous fibroids.

Dienogest therapy during the early stages of recurrence of endometrioma might be an alternative therapeutic option to avoid repeat surgeries.

AIM: We aimed to evaluate whether hormonal therapy immediately after postsurgical recurrence of ovarian endometrioma controls disease progression and can be an alternative therapeutic option to avoid multiple repeat surgeries. METHODS: We enrolled 146 patients treated for endometrioma at the University Hospital of Kyoto Prefectural University of Medicine between 2009 and 2015. After laparoscopic cystectomy using the stripping technique, opening of cul-de-sac obliterations and complete resection of the deep infiltrating endometriosis lesions, the patients either received no treatment (n = 83), oral contraceptives (OC; n = 32) or dienogest (DNG; n = 27), depending on their medical history. Four patients were excluded because they changed their regimens during the follow-up period. All patients were followed up every 3 months. Patients who developed recurrence of endometrioma immediately received DNG, OC or gonadotropin-releasing hormone agonist. RESULTS: Overall, 16 patients developed a recurrence of the endometrioma (12 in the nontreatment group, three in the OC group and one in the DNG group). The 11 patients with recurrence were treated with DNG immediately after the diagnosis of recurrent endometrioma. Among them, seven patients continued treatment with DNG (2 mg) for 24 months. After 24 months of treatment with DNG, complete resolution of recurrent endometrioma was achieved in four (57.1%) of seven patients. There was no improvement in the three patients who received OC and one patient who underwent secondary surgery. CONCLUSION: DNG therapy early after recurrence of postsurgical endometrioma appears to be viable for reducing the risk of repeated surgery.