Search

The epithelial ovarian carcinoma (EOC) is an aggressive malignant tumor, and is currently the leading cause of gynecologic cancer death. CA125 is the most commonly used serum marker for EOC, but shows a high-false-positive rate for several benign diseases such as endometriosis. The purpose of our study is therefore to identify a useful biochemical tool for detecting qualitative differences between CA125 from patients with endometriosis and EOC, and to facilitate differential diagnosis of these diseases. In our study, using two different CA125-binding molecules, i.e., recombinant mesothelin and an anti-CA125 monoclonal antibody, a novel sandwich ELISA for determining the serum levels of CA125 with mesothelin-binding ability (CA125meso) was developed, and tested for patients with endometriosis ( n = 59) and EOC ( n = 36). We found that both the serum CA125meso level and the ratio of the serum CA125meso to CA125 levels (CA125meso/CA125) were significantly higher in patients with EOC than in patients with endometriosis ( p < 0.00005 and p < 0.000001, respectively). Furthermore, receiver operating characteristic analysis showed that the CA125meso assay was superior to the conventional antibody-based CA125 assay in discriminating endometriosis from EOC. Thus, mesothelin-binding ability may be a useful indicator for qualitatively evaluating CA125 in patients with endometriosis and EOC. [ABSTRACT FROM AUTHOR]

The Japan Society of Obstetrics and Gynecology Reproductive Endocrinology Committee summarizes the activities of each subcommittee below from April 2011 to March 2013. Survey for clinical outcomes of infertility treatment for women with adenomyosis and complications of pregnant women with adenomyosis., Survey for multiple pregnancies after controlled ovarian stimulation in non-assisted-reproductive-technology infertility treatment cycles: population-based study in Japan., Study on the effect of endometriosis management on ovarian reserve. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Although low serum testosterone (T) is associated with metabolic disorders, the mechanism of this association is unclear. The objective of the present study was to investigate the combined effects of T deficiency and a high-fat diet (HFD) on hepatic lipid homeostasis in mice. Materials/Methods: Orchiectomized (ORX) mice and sham-operated (SHAM) mice were randomly divided into five groups: SHAM mice fed a standard diet (SD), SHAM mice fed HFD, ORX mice fed SD, ORX mice fed HFD, and ORX mice fed HFD with T supplementation. After 4weeks of treatment, we investigated the synthesis and secretion of lipids in the liver and detailed serum lipoprotein profiles in each group. Results: ORX mice fed HFD showed increased hepatic steatosis, markedly decreased serum triglyceride (TG) and TG-VLDL content, and increased serum very small-LDL content. Gene expression analysis revealed that ORX mice fed HFD showed significantly decreased expression of microsomal triglyceride transfer protein, lipin-1, peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ coactivator 1-α, and significantly increased sterol regulatory element-binding protein-1, diacylglycerol acyltransferase-2 and fatty acid synthase. Reduction of hepatic AMPK phosphorylation was observed in ORX mice fed HFD. These perturbations in ORX mice fed HFD were normalized to the levels of SHAM mice fed HFD by T supplementation. Conclusion: T deficiency is associated with failure of lipid homeostasis mediated by altered expression of genes involved in hepatic assembly and secretion of lipids. [Copyright &y& Elsevier]

Background/Aims: The senescence marker protein-30 (SMP30) is a 34 kDa protein originally identified in rat liver that shows decreased levels with age. Several functional studies using SMP30 knockout (Smp30Y/−) mice established that SMP30 functions as an antioxidant and protects against apoptosis. To address the potential role of SMP30 in nonalcoholic fatty liver disease (NAFLD) pathogenesis, we established Smp30Y/− mice on a Leprdb/db background (Leprdb/dbSmp30Y/− mice). Research Design/Principal Findings: Male Leprdb/dbSmp30Y/− mice were fed a standard diet (340 kcal/100 g, fat 5.6%) for 16 weeks whereupon the lipid/lipoprotein profiles, hepatic expression of genes related to lipid metabolism and endoplasmic reticulum stress markers were analyzed by HPLC, quantitative RT-PCR and western blotting, respectively. Changes in the liver at a histological level were also investigated. The amount of SMP30 mRNA and protein in livers was decreased in Leprdb/dbSmp30Y/+ mice compared with Leprdb/+Smp30Y/+ mice. Compared with Leprdb/dbSmp30Y/+ mice, 24 week old Leprdb/dbSmp30Y/− mice showed: i) increased small dense LDL-cho and decreased HDL-cho levels; ii) fatty liver accompanied by numerous inflammatory cells and increased oxidative stress; iii) decreased mRNA expression of genes involved in fatty acid oxidation (PPARα) and lipoprotein uptake (LDLR and VLDLR) but increased CD36 levels; and iv) increased endoplasmic reticulum stress. Conclusion: Our data strongly suggest that SMP30 is closely associated with NAFLD pathogenesis, and might be a possible therapeutic target for NAFLD. [ABSTRACT FROM AUTHOR]

We report a pregnant woman with symptomatic deep venous thrombosis of the lower extremity distributing in the left iliac, femoral, popliteal and calf veins. Systemic anticoagulation therapy failed; however, treatment was successful through a combination of various endovascular procedures, including catheter-directed thrombolysis. During the therapies, an optional inferior vena cava filter was implanted to protect against the development of pulmonary embolism. [ABSTRACT FROM AUTHOR]

Introduction: Cervical dilatation and/or uterine evacuation and curettage (D/E&C) is the most commonly performed and safest gynecological procedure. Although procedure-related uterine perforation is rare, this condition may require surgical intervention. Ultrasound examination and computed tomography are useful for diagnosing such perforations with incarceration of an intra-abdominal organ. However, the use of magnetic resonance imaging (MRI) for detecting postabortal uterine damage has seldom been discussed in the literature. Case report: A 31-year-old woman was referred to our department for lower abdominal pain and a small amount of vaginal bleeding 28 days after D/E&C for a missed abortion. Transvaginal ultrasound examination showed the presence of a hyperechogenic structure in the anterior wall of the uterine body, which was verified to be fatty tissue by MRI, particularly on the fat-suppressed T1-weighted images. An emergency laparotomy showed a uterine perforation with omentum incarceration. After dissecting the omental loop, the uterine perforation site was incised, and the involved omental tissue was debrided appropriately. Discussion: To our knowledge, this is the first report wherein MRI was used for the detection of incarcerated omental fat within the uterus. Delayed presentation of uterine perforation may be observed 1 month or more after D/E&C, although such a finding is extremely rare. Therefore, postabortal follow-up bimanual vaginal examination using transvaginal ultrasonography is recommended. The current study indicates the usefulness of MRI when myometrial perforation with or without incarceration of an extrauterine organ is suspected. [ABSTRACT FROM AUTHOR]

BACKGROUND Our aim was to study ways to improve IVF success rates in women with suspected endometrial receptivity defects. METHODS We conducted a retrospective cohort study examining the effect of letrozole (aromatase inhibitor) on integrin expression as a marker of endometrial receptivity. We compared IVF outcomes in 97 infertile women who had undergone ανβ3 integrin assessment by immunohistochemistry in mid-luteal endometrial biopsies. Of 79 women undergoing standard IVF, 29 (36.7%) lacked normal integrin expression. Eighteen other women with low integrin were studied after receiving letrozole during early IVF stimulation. An independent set of ανβ3 integrin-negative patients (n = 15) who had undergone repeat endometrial biopsy for integrin testing while taking letrozole were re-evaluated. RESULTS Clinical pregnancy and delivery rates were higher in women with normal ανβ3 integrin expression compared with those who were integrin negative [20/50 (40%) versus 4/29 (13.8%); P = 0.02 and 19/50 (38%) versus 2/29 (7%); P < 0.01, respectively]. In 18 women who received letrozole early in IVF, 11 conceived (61.1%; P < 0.001) compared with integrin-negative patients who did not receive letrozole. In integrin-negative women who were rebiopsied on letrozole, 66.7% reverted to normal integrin expression. Positive endometrial aromatase immunostaining using a polyclonal antibody was a common finding in infertile patients compared with controls. CONCLUSIONS Lack of endometrial ανβ3 integrin expression is associated with a poor prognosis for IVF that might be improved with letrozole co-treatment. Prospective studies are needed to confirm and extend these findings but the data suggest that aromatase expression may contribute to implantation failure in some women. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To examine whether long-term administration of dienogest following gonadotropin-releasing hormone agonist (GnRH-a) therapy would prolong the relief of pelvic pain while reducing the amount of irregular uterine bleeding. Study design: This was a prospective, non-randomized clinical trial. Among the patients suffering from chronic pelvic pain associated with recurrent endometriosis, Group G (n =38) received GnRH-a for 4–6months and then dienogest (1mg/day) for 12months. The dose of dienogest was increased to 1.5 or 2mg/day when a patient had uncontrollable uterine bleeding {n =15 (39%)}. Group D (n =33) received only dienogest (2mg/day) for 12months. Pelvic pain was assessed using a visual analog scale (VAS). Uterine bleeding was semi-quantified using a pictorial blood loss assessment chart (PBAC). Results: In Group G, GnRH-a significantly reduced the VAS score for pelvic pain, and alleviation was maintained during the 12-month therapy with dienogest. There was no significant difference in pain reduction between Group G and Group D. The PBAC score during the first 6months on dienogest was significantly smaller in Group G than in Group D. Conclusion: Treatment with a GnRH-a followed by long-term dienogest therapy maintains the relief of endometriosis-associated pelvic pain achieved with GnRH-a therapy for at least 12months. This regimen reduces the amount of irregular uterine bleeding that often occurs during the early phase of dienogest therapy. [Copyright &y& Elsevier]

Abstract: Estrogen replacement in postmenopausal women may help prevent or delay development of Alzheimer''s disease. Because loss of basal forebrain cholinergic neurons with reductions in choline acetyltransferase (ChAT) concentration are associated with Alzheimer''s disease, we investigated the effect of estradiol (E2) and J 861, a non-feminizing estrogen, on cholinergic neurons in the basal forebrain. Ovariectomized rats received E2, J 861 or vehicle, and basal forebrain sections through the substantia innominata, medial septum, and nucleus of the diagonal band were immunostained for ChAT. ChAT-immunoreactive cells in the basal forebrain were significantly reduced in the ovariectomized rats compared to intact rats, but those ovariectomized rats receiving estrogen replacement with E2 and J 861 had near normal levels of ChAT-positive neurons. While retrograde tracing experiments with fluorogold injected into the prefrontal cortex showed no significant differences in the number of fluorogold-labeled cells among the groups, ChAT-immunoreactive cells and double-labeled cells were significantly lower in OVX rats than in intact and E2 rats. Some substantia innominata cells in the J 861 rats were ChAT/estrogen receptor α-positive. These results suggest that E2 and J 861 have positive effects on cholinergic neurons that project from the basal nucleus to the forebrain cortex. [Copyright &y& Elsevier]

Objective:The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear hormone receptor that plays an important role in many diseases. This study investigated whether two polymorphisms (Pro12Ala in exon B and C161T in exon 6) of the PPAR-γ2 gene are related to adenomyosis, endometriosis, or leiomyomata.Methods:A total of 390 patients with adenomyosis, endometriosis, and/or leiomyomata were classified into four groups: 103 patients with adenomyosis (21 adenomyosis only and 82 adenomyosis with endometriosis and/or leiomyomata), 95 patients with endometriosis only, 100 patients with leiomyomata only, and 92 patients with endometriosis and leiomyomata.Results:There was no association between distribution of genotype or allele frequencies for the PPAR-γ Pro12Ala polymorphism and the presence of adenomyosis, endometriosis, and/or leiomyomata. However, compared with results for controls, the PPAR-γ 161CC genotype and 161C allele frequencies were significantly increased in patients with adenomyosis (genotype: χ2 = 9.185, corrected P value [Pc] = .0169; allele: χ2 = 8.337, Pc = .0155) and in patient with endometriosis (genotype: χ2 = 6.748, Pc = .0375; allele: χ2 = 6.413, Pc = .0453).Conclusion:The results suggest that the PPAR-γ 161CC genotype could be a genetic risk factor for adenomyosis and endometriosis, whereas the Pro12Ala polymorphism was not associated with these estrogen-dependent benign uterine diseases in a Japanese population. [ABSTRACT FROM PUBLISHER]

PROBLEM: Tumor necrosis factor (TNF)-α is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region (TNFA ) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic susceptibility to endometriosis. METHODS OF STUDY: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR)-preferential homoduplex formation assay and PCR-restriction fragment length polymorphism, respectively. RESULTS: The frequency of the TNFA-U01 haplotype was increased significantly in patients with endometriosis compared with controls (P = 0.045, OR =1.45). The TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was found in TNFR2 polymorphism between patients and controls. CONCLUSION: Our results indicated that NFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA-class I polymorphisms. [ABSTRACT FROM AUTHOR]

Peritoneal loose bodies (PLBs) are defined as fibrotic or calcified-free bodies within the peritoneal cavity; they commonly autoamputate from appendices epiploicae that have undergone torsion. Pedunculated, subserosal uterine leiomyomas (PSULs) are subserosal uterine leiomyomas connected to the uterus via a pedicle. In the present report, we describe the case of a PLB that originated from the autoamputation of a PSUL, confirmed based on histological evidence consistent with a uterine leiomyoma and the laparoscopic findings of a broken pedicle. This case clearly demonstrates the potential for a uterine leiomyoma to be the source of a PLB. Our findings contribute to the understanding of the etiological relationship between PLBs and uterine leiomyomas. [ABSTRACT FROM AUTHOR]

Objectives: We collected real-world data on the safety and clinical outcomes of the levonorgestrel-releasing intrauterine system (LNG-IUS) for heavy menstrual bleeding and dysmenorrhea.Study Design: This was a prospective, multicenter, single-cohort, open-label, post-authorization 12-month follow-up study of Japanese patients initiating the LNG-IUS for heavy menstrual bleeding and/or dysmenorrhea. The primary endpoint was the safety profile based on adverse events and adverse drug reactions (ADRs), including expulsions and abnormal bleeding, within 12 months of LNG-IUS insertion. Secondary endpoints included changes from baseline in menstrual blood loss based on bleeding days and dysmenorrhea graded on a visual analog scale (VAS).Results: Of the 595 patients included, many had underlying conditions such as adenomyosis (39.5%), uterine leiomyoma (30.8%), or endometriosis (12.9%). The incidences of ADRs and serious ADRs were 59.7% and 0.3%, respectively. Frequently reported ADRs were metrorrhagia (48.9%), procedural pain (14.1%), and ovarian cyst (6.2%). The cumulative incidence of expulsions at 12 months was 8.7%. Risk factors for expulsion were obesity (body mass index ≥25 kg/m2), adenomyosis, and uterine cavity length ≥8 cm. The median [interquartile range] VAS score for dysmenorrhea improved from 46.5 [13.0-68.0] at insertion to 1.0 [0.0-13.0] at 12 months, and improvements were also observed in chronic pelvic pain and painful defecation.Conclusions: The LNG-IUS safely and effectively reduced dysmenorrhea, chronic pelvic pain, and painful defecation. Risk factors for expulsion suggest that patients with underlying organic disease should be monitored carefully when using the LNG-IUS.Implications: The LNG-IUS is an effective treatment for secondary dysmenorrhea with organic disease, and for the reduction of chronic pelvic pain; however, physicians should be aware of the increased risk of expulsion in patients with organic conditions. [ABSTRACT FROM AUTHOR]